The Relation of 'Fletcher Factor' to Factors XI and XII

S ummary . Further evidence is presented for the existence of a new coagulation factor which is closely related to Hageman factor (XII) and plasma thromboplastin antecedent, PTA (XI). This factor has been tentatively designated 'Fletcher factor'. Coagulant activity of Fletcher factor was separated from the clotting activity of factors XI and XII by C-M Sephadex column chromatography of intact normal plasma. Other studies showed that the prolonged partial thromboplastin time or plasma recalcification time of Fletcher-deficient plasma could be 'corrected' by prolonged contact with celite, glass, kaolin, or ellagic acid; all are known activators of factor XII. Cytochrome c, known to inhibit the contact activation of factor XII, completely abolished this contact 'correction' of Fletcher-deficient plasma. Thus, the clotting times of plasmas deficient in Fletcher factor (presently found in seven individuals from four unrelated families) are readily corrected by activated factors XII and XI. None of these individuals has any bleeding tendencies.
Fletcher factor activity is deficient in the plasma of newborn infants; the factor is probably produced in the liver and not dependent on vitamin K for its synthesis.     

Studies on Serum and Infectious Hepatitis Viruses of Man

A preliminary report of the results so far describe briefly the recovery of the serum hepatitis virus from five human volunteers who acquired serum hepatitis after inoculation with prototype B SH virus and from one patient acutely ill with (presumably transfusion caused) serum hepatitis, as well as the recovery of IH virus from two patients acutely ill with infectious hepatitis. In all instances the SH and IH viruses have been passaged six to 13 times in stable lung cell tissue culture with a different but characteristic cytopathologic effect for the SH and IH viruses. Titration of the SH viruses showed that the TCID50, per ml. ranged from 10^-4.5 to 10^-6.0 per ml. and the IH from 10^-5.5 to 10^-6.6. Neutralizing antibodies against two SH viruses were produced in rabbits and against one IH virus in the guinea pig. A definite serological relationship has been established by neutralization tests between the virus from one of the SH volunteers and the virus from the patient with SH; between the two IH viruses; and between the SH and the IH viruses. The identity of the SH virus isolate from one of the volunteers was demonstrated by the production of neutralizing antibodies in a rabbit inoculated with NIH plasma pool #6, although attempts to grow virus from the plasma pool failed. The SH viruses are not inactivated by heating at 60 C. for four to six hours, the IH viruses are. SH virus killed mice and was recovered in tissue culture from their livers. IH virus did not infect mice. Both viruses have been grown also in trypsinized rabbit, guinea pig and hamster kidney tissue cultures and in human embryonic tissue cultures. Neither virus will grow in monkey kidney, ruling out most other enteric and adenoviruses of human origin. Further reports will be made as the studies continue.     

Benign symmetric lipomatosis: functional sympathetic denervation of adipose tissue and possible hypertrophy of brown fat

Levels of lipolytic hormones (growth hormone, cortisol, and glucagon), insulin, and free fatty acids were measured in a patient with benign symmetric lipomatosis during a 5-hr glucose tolerance test, an insulin tolerance test, a 24-hr fast, and an epinephrine infusion. Although there was no abnormality in insulin dynamics or impairment in lipolytic hormone secretion, there was a failure of free fatty acid concentrations to rise to expected levels during fasting and after glucose. Insulin hypoglycemia and epinephrine infusion resulted in normal and excessive free fatty acid responses, respectively. This pattern of free fatty acid release is consistent with functional sympathetic denervation of adipose tissue. The lipomatous fat in benign symmetric lipomatosis is similar in distribution to the brown fat of human newborns and rodents that may hypertrophy after denervation. It is suggested that the lipomas in this disorder may represent such brown adipose tissue.     

Primary meningococcal pericarditis: a disease of adults associated with serogroup C Neisseria meningitidis

Pericarditis due to Neisseria meningitidis is usually a consequence of meningeal disease or meningococcemia. This presentation includes a case report of primary meningococcal pericarditis (PMP) and a review of the clinical and epidemiologic features of 15 previously reported cases. All cases have been reported in the past 15 years. Most patients were older teenagers or adults. The median age and age distribution of PMP cases in the United States were significantly greater than that of patients with other meningococcal diseases reported to the Centers for Disease Control (CDC) (P = .005). Similarly, serogroup C N. meningitidis was isolated from 88% of U.S. patients with PMP, compared with isolation from 22% of patients with other meningococcal diseases reported to the CDC (P = .00016). Culture of pericardial fluid usually yielded meningococci, and most patients presented with signs and symptoms typical of purulent pericarditis. A positive pericardial culture was associated with the development of cardiac tamponade (P = .03). With appropriate antibiotic treatment and drainage of pericardial fluid when indicated, all 16 patients survived and experienced few or no sequelae.