Synthesis of endogenous pyrogen by rabbit leukocytes.

Rabbit ieukocytes from peritoneal exudates and from blood were stimulated to form leukocyte pyrogen in the presence of radiolabeled amino acids. The stimuli used were endotoxin, phagocytosis, and tuberculin. The crude leukocyte pyrogen samples were purified; pyrogen from exudate cells was rendered homogeneous; pyrogen from blood cells was still contaminated with other proteins. All the purified pyrogens were radioactive; and for all it was shown that radioactivity and pyrogenic activity coincided on electrophoresis at pH 3.5 and pH 9 in acrylamide and on isoelectric focusing in acrylamide. Furthermore, pyrogens obtained from exudate cells stimulated in different ways, or from blood cells and exudate cells stimulated with endotoxin, appeared to be identical. These results suggest that leukocyte pyrogen was synthesized de novo from amino acid precursors and that leukocytes made the same pyrogen whatever the stimulus used to activate them.

Renal manifestations of the staphylococcal toxic-shock syndrome.

Twenty-three women of ages 13 to 44 years were hospitalized with illnesses fulfilling the criteria of the case definition for the toxic-shock syndrome (TSS) associated with coagulase-positive staphylococci. Disease onset occurred during menses in 22, and all were oliguric when admitted. Prolonged hypotension and a reduced central venous pressure were common features. Measurements of urine volume and creatinine clearance in eight patients identified two types of acute renal failure, oliguric and nonoliguric, and prerenal azotemia related to intravascular volume depletion. Urinary sodium excretion and measurement of the renal index (UNa divided by U/PCr) provided further support for the presence of both prerenal and intrinsic renal failure. Hemodialysis was required in one patient in whom findings on renal nuclide scan were consistent with acute tubular necrosis. Pyuria was frequent, but proteinuria and more than five erythrocytes per high-power field were infrequent. Other features included initial hyponatremia and the combination of hypoproteinemia, hypoalbuminemia, hypocalcemia and hypophosphatemia of several days' duration. The hypoalbuminemia was believed to be due to exudation of protein from the intra- to the extravascular space. The hypoalbuminemia was believed to be due to exudation of protein from the intra- to the extravascular space. The hypocalcemia was probably related to the hypoalbuminemia. The pathogenesis of hypophosphatemia in the presence of acute renal failure is unclear. Following the intravenous administration of colloids, fluids and, in seven patients, dopamine, all recovered from the acute illness.

Hypoglycorrhachia and coxsackie B3 meningoencephalitis.

The case of a 3-week-old infant with Coxsackie B3 meningoencephalitis is discussed. Hypoglycorrhachia and neutrophils in the cerebrospinal fluid characterized the first ten days of her illness. Coxsackie B3 should be added to the list of enteroviruses that can cause hypoglycorrhachia during infections of the central nervous system in children.

Staphylococcus aureus cellulitis: an unusual presentation.

Staphylococcus aureus has long been known as one of the most virulent microbes, with capabilities that make it threatening in both nosocomial and community-acquired infections. It remains the most frequent cause of skin-structure and traumatic infections in the community. S. aureus infections in the maxillofacial region are likely to be associated with a known portal of entry, but this is not always the case. Once invasion occurs, the organism may produce virulent enzymes including coagulase, hyaluronidase, proteases, DNA-ase, lipases, hemolysins, and lysozyme as well as exotoxins. Markel et al point out that cellulitis associated with coagulase-positive staphylococci will often resolve without abscess formation. Hence, there is often no site from which to obtain specimens, making this infection a diagnostic and therapeutic challenge. This report describes an infection in which the etiologic organism was identified as S. aureus. The source of the infection, however, remained unclear.

Toxic-shock syndrome: a commentary and review of the characteristics of Staphylococcus aureus strains.

Toxic-shock syndrome (TSS) was first identified in 1978 in children as a toxin-mediated illness associated with Staphylococcus aureus. Extensive publicity ensued when the strong association of this disease with menses and tampon use was recognized in 1980. Since that time, investigation into the epidemiology, clinical manifestations and pathogenesis of TSS has coincided with a decreasing incidence of disease. A unique exotoxin has been isolated under varying physico-chemical conditions from TSS-associated strains of S. aureus and its effect on immune function and other parameters both in vitro and in vivo described. In addition, TSS-associated S. aureus strains have been found to have characteristic heavy metal susceptibility patterns, to be lysogenized and to show decreased hemolysis on sheep blood agar. Preliminary results of the prevalence of TSS-associated strains of S. aureus and of the theories of pathogenesis are reviewed.

Candida meningitis in newborn infants: a review and report of combined amphotericin B--flucytosine therapy.

Meningitis due to Candida albicans was successfully treated in a 1.1 kg premature infant using combined antifungal therapy of amphotericin B for three weeks and 5-fluorocytosine for four months. Hydrocephalus and profound psychomotor retardation were present one year later. Psychomotor retardation, aqueductal stenosis and hydrocephalus were found to be common in a review of 16 previously reported cases of central nervous system (CNS) candidiasis in newborn infants. The diagnosis and institution of therapy were frequently delayed, and the mortality rate was 29% in the 17 patients reviewed here. The subacute course, lack of clinical findings, variable cerebrospinal fluid (CSF) findings, negative CSF cultures due to low concentrations of organisms, slow in vitro growth of C. albicans and misinterpretation of positive cultures as contaminants are factors frequently leading to delayed diagnoses. Using combination therapy, it should be possible to use lower doses and shorter courses of amphotericin B therapy for C. albicans meningitis in the newborn infant.

The disease spectrum, epidemiology, and etiology of toxic-shock syndrome.

From this composite picture of the history and recent developments related to TSS, several points are clear. TSS is not a new disease, and TST-producing strains of S. aureus are not new. What is new is the recent dramatic increase of this disease in young women who use tampons during menses and who lack antibody to TST. What is also new is the recognition that the disease commonly recurs but only in menstrually associated cases. What remains to be determined are the precise role of tampons, the factors leading to toxin induction, and the mechanism of action of this potent toxin. In order to better determine what these factors and mechanism of action are, and to determine if the TST marker protein is in fact the critical toxin, a reliable animal model is badly needed. Finally, a reliable laboratory test to confirm the clinical diagnosis is another high-priority need. The further unraveling of the secrets of this complex disease may greatly enhance our understanding of the disease associated with this toxin, of the intricacies of toxin production by other bacteria, and of the role that exogenous cofactors play in disease processes.

Detection of a second widespread strain of Epstein-Barr virus.

The prevalence of Epstein-Barr virus (EBV) type B, which was previously found mainly in equatorial Africa, was investigated with the polymerase chain reaction in a population of healthy adults in Memphis, Tennessee. EBV was detected in the throat washings of 34 (22%) of 157 randomly selected donors, 14 (41%) of whom had type B virus and 17 (50%) type A; 3 donors (9%) had both strains. 18 additional adults with human immunodeficiency virus (HIV-1) infection and 6 severely immunocompromised children were also investigated. Results indicated that type B EBV is widespread in nature and may be reactivated by immunodeficiency.

Outer membrane protein subtypes and investigation of recurrent Haemophilus influenzae type b disease.

Ten previously healthy patients, ages 3 to 26 months, developed recurrent episodes of deep-tissue Haemophilus influenzae type b infections from 4 to 191 days (median = 28 days) after the last day of antibiotic therapy given for the first episode. None of the patients had a persistent focus of infection and eight were considered to have had adequate therapy for the initial episode. Bacteremia, without evidence of relapse at the site of the original infection, was documented in eight of the ten recurrent episodes. The ampicillin susceptibilities of the HITB isolates changed between episodes in two of the patients. Blood or CSF isolates from both episodes in seven patients were examined for biotypes and outer membrane protein subtypes. Concordance of both biotype and OMP subtype was present for all seven paired isolates, including the two pairs in which the HITB ampicillin sensitivities had changed. These data imply that some patients become reinfected with their original HITB isolates and that OMP and capsular antigens do not always elicit protective immunity, even after natural infection.

Acute cholestasis in patients with toxic- shock syndrome.

Serum liver function tests were performed in 22 females fulfilling the criteria for toxic-shock syndrome. All patients showed evidence of hepatic dysfunction during their hospital course. These findings included hyperbilirubinemia in the absence of laboratory evidence for significant hemolysis, mold elevation of the transaminases, threefold increase in their serum bile salt concentration, and hypoalbuminemia. These findings are best explained by hypoperfusion of the liver and a canalicular injury secondary to staphylococcal exotoxin. Cholestasis appears to be a universal finding in toxic-shock syndrome.

Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention.

Surveillance for toxic-shock syndrome (TSS) in Wisconsin detected 38 cases with onsets from September 1975 through June 1980. Thirty-seven of the cases occurred after January 1, 1979; 37 of the patients were women, 35 cases occurred during menses; 38 patients were white; and one patient died. Cervical or vaginal cultures were obtained before antibiotic therapy in 23 patients, and 17 cultures were positive for Staphylococcus aureus. Ten patients had at least one recurrent episode during subsequent menstrual periods. The recurrence rate was lower in patients who had been treated with beta-lactamase-resistant antibiotics. Thirty-five patients were matched for age and menstruation to 105 controls: 34 of 35 cases (versus 80 of 105 controls) used tampons during every menstrual period (P < 0.01); nine of 35 cases (versus 64 of 105 controls) practiced contraception (P < 0.001). In Wisconsin the minimum incidence of TSS as defined by clinical criteria is 6.2 cases per 100,000 menstruating women per year. The rate of TSS among menstruating women younger than 30 years was 2.4 to 3.3 times the rate among those who were 30 or older.

Demineralization in cystic fibrosis detected by direct photon absorptiometry.

Bone mineral content, bone width, and their ratio were measured in patients with cystic fibrosis (CF) using monoenergetic photon absorptiometry. Serial measurements of the radius and ulna were made in 27 patients with CF and were compared with 968 age-matched controls. Demineralization was found in 37% of the boys and 63% of the girls. Patients under age 10 years had normal bone mineral content and nine of 15 patients aged 13 or older were demineralized (P less than .01). Demineralization correlated with the extent of weight reduction in patients (P less than .001). Patients most likely to be demineralized were adolescent girls. To our knowledge, this is the first report of bone mineral status of children with CF, and the results indicate that a sizable proportion of these patients may be demineralized without overt rickets.