A. M. Lerner

Passive hemagglutinatíng antibodies in cerebrospinal fluids in herpesvirus hominis encephalitis.

Summary Passive hemagglutinating antibodies (PHA) to herpesvirus hominis were assayed in spinal fluids obtained during illnesses in seven patients with herpesvirus encephalitis. There were five cases in adults due to type 1 virus, and two perinatal type 2 infections. CSF-PHA were present in each case. Antibodies in CSF were IgM in the neonatal cases, but predominantly IgG in the rest. PHA in spinal fluid do not correlate with degree of meningeal injury as indicated by pleocytoses or protein. Kinetics of rises in PHA in spinal fluids and sera suggest that the antiherpesvirus antibodies in the central nervous system may be locally produced. PHA to herpesviruses were virtually absent in spinal fluids of 35 control patients with various conditions requiring lumbar puncture.

Differential Sensitivity of Herpes Simplex Virus Types 1 and 2 to Human Interferon: Antiviral Effects of Interferon plus 9-β-d-Arabinofuranosyladenine

With use of a standard assay for antiviral compounds, in which the compound to be tested is added after absorption of virus, the minimal inhibitory concentration (MIC) of human interferon for several strain of herpes simplex virus type 2 (HSV-2) is five to 10 times greater than it is for two strains of herpes simplex virus type 1 (HSV-1). This differential susceptibility of HSV types to interferon is found whether tests are done with a liquid overlay and microtiter plates or with agarose overlays and appears to be a distinguishing biological marker. When the MIC of interferon is tested by microtiter or agarose methods and interferon is allowed to incubate for 24 hr before virus is added, values for HSV-1 and HSV-2 are similar and much smaller in magnitude. These results support earlier data indicating that adenine arabinoside and interferon are synergistic against herpes simplex virus type 1 in vitro and indicate that these agents are additive but not synergistic against herpes simplex virus type 2.

Xeroradiographic, Bacteriologic, and Pathologic Studies in Experimental Staphylococcus Osteomyelitis

Summary Detailed roentgenographic, pathologic, and bacteriologic findings of a widely used rabbit model of staphylococcus osteomyelitis have not been reported. We induced post-traumatic staphylococcus tibial osteomyelitis in 25 young New Zealand rabbits. Abscesses formed at sites of inoculation, and infection spread contiguously, both superiorly and caudally to eventually involve the entire tibia. An outer advancing zone of edema was followed by an inflammatory mid-zone and a proximal zone of abscess. Progressive bony destruction produced pathologic fractures, sequestra, and involucra. By the 20th day of infection, the entire bony architecture was replaced by contiguous abscesses. Serial xeroradi-ographs correlated well with progressing pathologic findings. A definitive radio-graphic diagnosis was possible on the fifth day of infection.

Coxsackievirus b3-positive mononuclear leukocytes in peripheral blood of swiss and athymic mice during infection.

Abstract Coxsackievirus B3 viremia in infected 14-day-old Swiss and young adult Nude mice is predominantly a plasma viremia. Despite high titers of virus in plasma, separated suspensions of red blood cells and polymorphonuclear leukocytes contain no virus. Virus-positive mononuclear leukocytes in blood, on the other hand, may be present from the second to the fourth days of infection. Virus-positive mononuclear leukocytes may persist after virus is no longer in the plasma. Our studies do not definitively identify the mononuclear population in blood which is virus-positive.

Absence of idoxuridine and persistence of herpes simplex virus in brains of patients being treated for encephalitis.

Summary Thirty-two specimens of brain from five patients with encephalitis suspected to be caused by herpes simplex virus, type 1 (HSV-1) were assayed for antiviral activity. Each patient received 60-80 mg/kg/day of idoxuridine (IDU) by intravenous infusion. The antiviral assay does not measure anti-HSV-1 antibodies. Biopsies of brain in every patient taken before IDU was used, and portions of several regions of the brain at autopsy were available during courses of treatment in four of the five patients. The last patient died 7 days after completing treatment. A significant concentration of IDU (833 μg/ml) was measured transiently in the cerebrospinal fluid of one patient. Meninges and brains showed inflammatory changes. Within the sensitivity of the test (≧ 6 μg/g) all specimens contained no IDU. As given, IDU does not achieve therapeutic concentrations in human brain. Further clinical use of IDU in therapy of herpes simplex virus encephalitis is not indicated. Aided by Grants from the National Institute of Allergy and Infectious Diseases (No. AI 00261-11), the National Institute of Neurological Diseases and Stroke (No. NS 11455-05) and another from the Skillman Foundation for the general support of research in Infectious Diseases at Wayne State University.

Elevated thymocyte norepinephrine and cyclic guanosine 3′,5′ monophosphate in T-lymphocytes from exercised mice with coxsackievirus B3 myocarditis☆

Abstract On the ninth day after coxsackievirus B3 infection in adolescent ICR Swiss mice, norepinephrine levels in the thymus in infected-swum mice (Group III) were significantly greater than those in infected (Group II) but not exercised controls. Similarly, levels of thymocyte cyclic 3′,5′ guanosine monophosphate were elevated. After isoproterenol, thymocytes from exercised, healthy, uninfected mice (Group IV) generated enhanced levels of cyclic 3′,5′ adenosine monophosphate, but beta stimulated thymocytes from mice in Group III fail to raise levels of cyclic 3′,5′ adenosine monophosphate. Rises in T-lymphocyte norepinephrine and cyclic 3′,5′ guanosine monophosphate accompany a concomitant decrease in cyclic 3′,5′ adenosine monophosphate in CB3-infected and swum mice.

An Enterovirus-Induced Murine Model of an Acute Dilated-Type Cardiomyopathy

After coxsackievirus B3 (CB3) infection of mice, migration of transfused sensitized and nonsensitized 51Cr-labelled T lymphocytes was followed. At autopsies on days 5.5, 6, 7, and 9 after infection, T-cell-dependent in situ calcification was assessed by cardiac xeroradiographs. In CB3-infected animals from group 2 that were not forced to swim (Gr. 2, Inf +, Ex -), significant rerouting of sensitized 51Cr-labelled T cells to the heart occurred beginning on the 9th day after infection. This was accompanied by myocardial calcification. When mice with CB3 myocarditis were forced to swim (Gr. 3, Inf +), 4 times the density of sensitized 51Cr-labelled T cells was redirected to the heart. At xeroradiography, severe myocardial calcification was shown to accompany cardiac dilatation.

Studies of in vitro synergy between several beta-lactam and aminoglycoside antibiotics against endocarditis strains of Pseudomonas aeruginosa

Ten strains of Pseudomonas aeruginosa isolated from patients with endocarditis (1969-1975) and eight similar strains (1980) were assayed for minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) to several aminoglycosides (gentamicin, tobramycin, amikacin) and beta-lactam antibiotics (ticarcillin, piperacillin, azlocillin, moxalactam and MKO 787). In vitro synergy (1969-1975 series) between beta-lactam and aminoglycoside antibiotics was shown uniformly with azlocillin (100 per cent) followed by moxalactam (80 per cent), piperacillin and ticarcillin (66 per cent) and MKO 787 (13.3 per cent). Results were similar in 1980. Synergy of azlocillin was demonstrated with five strains previously not showing synergy between carbenicillin and an aminoglycoside. In 1980 four of eight patients infected with pseudomonads that were not synergistically affected in vitro were refractory to treatment with the piperacillin-aminoglycoside combination. In vitro synergy of the infecting strain is necessary for successful medical treatment of patients with P. aeruginosa infective endocarditis.

A cardiomyopathy of balb/c mice (superimposed infection by coxsackievirus b-3).

Summary We describe progressive cardiomyopathy affecting three, and probably all four substrains of BALB/c (C) mice examined. Cardiac changes are limited to the pericardium and immediately subjacent epicardium of the right ventricle. By 2 months of age, mice have mononuclear infiltrates which progress to a dense exudative pericarditis. Whitish flecks on the pericardial surface can be seen at 6 months, and a calcifying scar persists. When 103.5TCD50 of coxsackievirus B-3 (Nancy) is inoculated intraperitoneally into weanling Swiss or C3H mice, myocarditis without pericarditis results. If the infected mice are BALB/c, myocarditis and right ventricular pericarditis ensues. A calcified fibrotic scar over the right ventricle identical to the end-stage of the inherent lesion appears in coxsackievirus B3 infected mice at about one month of age. Coxsackievirus B-3 multiplies equally well in the right and left ventricles of C mice, but pericarditis is limited to the right heart. In age-matched controls, the prevalence of calcific right ventricular pericarditis in BALB/c mice inoculated with coxsackievirus B-3 is the same as that of the inherent cardiomyopathy, and it is possible that the early calcific lesion in infected mice occurs in animals who later would have developed a right ventricular pericardial cardiomyopathy.