Lowell A. Glasgow

The staphylococcal scalded-skin syndrome.

Abstract A syndrome of dermatologic response to infection with phage Group 2 coagulase-positive staphylococci with reactions ranging from bullous impetigo to generalized scarlatiniform rash without exfoliation to generalized exfoliative disease was observed in 17 children. Staphylococci isolated from these patients, as well as two additional Group 2 organisms, produced exfoliation in newborn mice. The experimental lesion progressed from the development of a Nikolsky sign to bullous formation and then widespread exfoliation. Histologic sections were characterized by a cleavage plane within the epidermis at the stratum granulosum. Among 36 strains, the capacity to produce exfoliation was unique to staphylococci of phage Group 2. The disease produced in newborn mice reproduces the scalded-skin syndrome. Staphylococci may be recovered from involved animals. Thus Kochs postulates are fulfilled, and staphylococci of phage Group 2 are established as the etiologic agent of this syndrome.

Staphylococcal scalded skin syndrome: the expanded clinical syndrome.

Twenty-eight patients with dermatologic reactions to infection with phage group II staphylococci are described. Reactions in the skin included: generalized exfoliative disease in infants (Ritters disease) and in children (toxic epidermal necrolysis), generalized scarlatiniform erythema without exfoliation (staphylococcal scarlet fever), and localized bullous impetigo. The generalized exfoliative disease in the newborn infant or in older chlidren and bullous impetigo have previously been associated with this particular organism, but nonstreptococcal scarlatiniform eruption has not. These various clinical manifestations of infection with the phage group II staphylococcus present a spectrum of disease with a single etiology. Utilizing an experimental model, methicillin therapy was demonstrated to be effective in ameliorating the course of the disease; treatment with corticosteroids had no beneficial effect.

Treatment of experimental herpesvirus infections with phosphonoformate and some comparisons with phosphonoacetate.

Phosphonoformate (PF) at a concentration of 5 to 10 μg/ml inhibited the growth of type 1 strains of herpes simplex virus (HSV) in tissue culture, whereas 20 to 30 μg/ml was required for inhibition of type 2 strains and about 50 μg/ml was required for murine cytomegalovirus. In mice inoculated intraperitoneally or intracerebrally with HSV or intraperitoneally with murine cytomegalovirus, treatment with 250 to 400 mg of PF per kg twice daily for 5 days had only minimal effectiveness. When mice were inoculated intravaginally (i.vg.) with HSV type 2 and treated i.vg. with 10% PF beginning 3 h after viral inoculation, treatment was effective in completely inhibiting viral replication in the genital tract. If i.vg. therapy was initiated 24 h after infection, when the mice had a mean virus titer of 105 plaque-forming units in vaginal secretions, a significant reduction in the mean virus titer was observed on days 3, 5, and 7 after infection as compared with control animals. In guinea pigs treated i.vg. with 10% PF beginning 6 h after i.vg. inoculation with HSV type 2 there was also complete inhibition of viral replication in the genital tract, and no extenal lesions developed. When therapy was initiated 24 h after infection there was a 4 to 5-log decrease in viral titers on days 3, 5, and 7 of the infection and a slight delay in the development of external lesions.

Comparison of antiviral and antitumor activity of activated macrophages

Abstract The antiviral and antitumor activity in vitro of normal, stimulated, vaccinia virus “immune”, and activated peritoneal macrophages were compared. Activated (pyran or corynebacteria induced) PEC exhibited both antitumor and antiviral activity. Stimulated (thioglyocollate) and vaccinia virus “immune” PEC inhibited virus growth but did not possess antitumor activity. Normal (unstimulated) PEC were relatively ineffective in either activity. The antiviral activity was nonspecific, being expressed against herpes simplex and EMC viruses in addition to vaccinia. Although a possible role for interferon was suggested by the lack of activity of mouse PEC on vaccinia virus growth in heterologous FLK cells, definitive proof was not obtained. The activity was most pronounced against multiple cycles of viral infection initiated at a low multiplicity of infection. Single cycle virus growth was not affected, suggesting that the major inhibition was on subsequent cycles of virus growth.

PSYCHOSOCIAL FACTORS MODIFYING HOST RESISTANCE TO EXPERIMENTAL INFECTIONS

We have attempted over the past six years to develop an animal “model” that would help elucidate the physiologic mechanisms by which psychologic and social factors influence host resistance to disease processes. In our work, numerous diseases and pathogens have been studied, though this report will include only those of an infectious or neoplastic nature. Our orientation from the onset has been that it cannot be predicted whether a specified experimental stimulation will increase, decrease, or not influence host resistance on any a priori grounds. Rather, it has been our view’ that whether or not a given form of stimulation is detrimental to the host depends upon the particular infectious agent (or disease process) to which the animal is subsequently subjected. Therefore, it seems best to avoid, whenever possible, the very use of the word “stress,” since it connotes, to many, a deleterious effect on the organism. It may be helpful to recall, as an analogy, that the stress of nutritional deficiency leads to decreased resistance to some microorganisms and increased resistance to others2 and that change in resistance is further complicated by the finding that the chronicity of the infection must be considered.3 The studies to be reported utilize one of three methods of modifying the animals’ environment: combinations of programmed light and electric shock stimulation, various forms of stimulation early in life, and differential housing. Under each of these conditions, the ability to change host resistance to a number of infectious agents will be discussed, and we also have included data from experiments using a transplantable rat tumor, Walker-256 sarcoma.

Viral myocarditis during pregnancy: Encephalomyocarditis virus infection in mice☆

Abstract The enhanced susceptibility of pregnant MLM-1 mice to EMC was studied. Virus multiplication in the brain was comparable in both pregnant and nonpregnant controls. EMC virus multiplied to higher levels in the hearts of pregnant mice. This was accompanied by myocarditis which was demonstrated histologically. Electrocardiograms of infected pregnant mice evidenced derangement in cardiac function. These findings suggest that involvement of the myocardium during EMC infection might account for the higher mortality rate during pregnancy.

Antiviral Activity of Extracts from Marine Algae

Extracts of two species of marine algae, Constantinea simplex and Farlowia mollis, were tested for antiviral activity in tissue culture and in experimental infections of mice. Treatment of confluent mouse embryo fibroblast cell monolayers with either compound before viral inoculation was effective in inhibiting the replication of herpes simplex virus type 1 and type 2, vaccinia virus, and vesicular stomatitis virus, but not encephalomyocarditis virus, Semliki Forest virus, or murine cytomegalovirus. Prophylactic administration of these extracts was effective in reducing final mortality or prolonging the mean day of death of animals inoculated by the intraperitoneal, intracerebral, or intranasal routes with herpes simplex virus type 2. When therapy was initiated after viral inoculation or at a site other than that of viral inoculation, no significant effect on mortality or on mean day of death was observed. Neither preparation was effective in mice inoculated intraperitoneally with encephalomyocarditis virus, Semliki Forest virus, or murine cytomegalovirus or in animals infected intravaginally with herpes simplex virus type 2. The prophylactic but not therapeutic antiviral activity of these preparations seriously limits their potential use in human herpes simplex virus infections.

THE STAPHYLOCOCCAL EPIDERMOLYTIC TOXIN: ITS ISOLATION, CHARACTERIZATION, AND SITE OF ACTION

The term “Ritter’s disease” stands as a tribute to the clinical acumen of Ritter von Rittershain, who in 1878 described a bullous exfoliative disease that affects newborn infants. His remarkable description of 287 infants seen in a foundling hospital in Prague remains the largest and most complete clinical description of this c0ndition.l By 1898, Winternitz had linked Ritter’s disease to infection with Staphylococcus aureus.2 A particular subgroup of coagulasepositive staphylococcus, those strains that belong to phage group 11, were identified as associated with Ritter’s disease by the early 1 9 6 0 ~ , ~ . A and since that time all outbreaks in which phage type has been reported have been associated with staphylococci of this phage group.

Optimal treatment of herpes simplex virus encephalitis in mice with oral acyclovir

The effect of oral or intraperitoneal administration of acyclovir was evaluated in four experimental models of herpes simplex virus (HSV) encephalitis in mice. Mice were inoculated with HSV-1 or HSV-2 intracerebrally or with HSV-2 intranasally, intraperitoneally, or intravaginally. With all four routes of inoculation, oral acyclovir therapy significantly reduced mortality when started as late as 72 to 96 hours after viral challenge. Intraperitoneal acyclovir was not effective in protecting mice inoculated intravaginally, but was effective if given 24 to 48 hours after intracerebral or intranasal challenge and as late as 96 hours after intraperitoneal infection. Oral acyclovir was more active than intraperitoneal treatment in all four model infections. Levels of acyclovir inhibitory for HSV in cell culture were maintained in plasma and brain tissue throughout oral treatment but lasted only three to six hours after each intraperitoneal treatment. These results suggest that acyclovir may be useful in treating serious HSV infections in humans.

Alteration of Mortality and Pathogenesis of Three Experimental Herpesvirus hominis Infections of Mice with Adenine Arabinoside 5′-Monophosphate, Adenine Arabinoside, and Phosphonoacetic Acid

The therapeutic effectiveness of adenine arabinoside 5′-monophosphate (ara-AMP), adenine arabinoside (ara-A), and phosphonoacetic acid (PAA) was compared in three experimental Herpesvirus hominis type 2 infections of mice. In animals inoculated with H. hominis by the intracerebral or intraperitoneal route, both ara-AMP and ara-A were highly effective in reducing mortality even when treatment was begun 48 to 96 h after viral inoculation. ara-AMP was the most effective in both models in that treatment could be initiated 24 to 48 h later in the course of infection than with ara-A and still confer significant protection. In mice inoculated intraperitoneally, protection due to ara-AMP therapy was associated with reduced replication of virus in visceral organs and complete inhibition of transmission of virus to the brain. PAA treatment of mice inoculated intraperitoneally was effective in reducing mortality only if initiated shortly after infection. Treatment with PAA did not reduce mortality of mice inoculated intracerebrally but did prolong the mean day of death. When mice were inoculated intranasally with H. hominis, none of the three drugs altered final mortality; however, treatment with ara-AMP did prolong the mean day of death. Treatment with ara-AMP effectively reduced viral replication in the lung and liver in this model infection, but failed to prevent transmission of virus through the trigeminal nerves from the nasopharynx to the brain.