The influence of cortisone on experimental viral infection. 8. Suppression by cortisone of interferon formation in mice injected with Newcastle disease virus.

The administration, of 5.0 mg of cortisone 6 to 24 hr prior to the intravenous injection of mice with NDV was associated with a marked reduction in the interferon response as measured in serum and spleen. Reduced concentrations of interferon following cortisone pretreatment were demonstrable from 6 to 16 hr following injection of virus.

An antiviral substance from Penicillium funiculosum. V. Induction of interferon by helenine.

Helenine, a substance obtained from broth cultures of Penicillium funiculosum and known to exert a protective effect in vivo in experimental animals against several unrelated viruses, has been shown to elicit the formation in cell cultures and in intact mice of an inhibitor of viral plaque formation. Because the biological and chemical characteristics of the viral inhibitor induced by helenine are similar to those of interferon, it is suggested that the antiviral effect of helenine may be mediated through the formation of interferon.

Long-term intravenous antibiotic therapy in chronic osteomyelitis.

Because the optimal treatment of chronic osteomyelitis is not well established, we studied the efficacy of prolonged (three months or more) outpatient intravenous antibiotic therapy via a Hickman catheter. Seventeen patients were entered into our protocol (13 with chronic osteomyelitis, three with chronic septic arthritis, and one with subacute osteomyelitis). Pseudomonas aeruginosa was the most common bone isolate, followed by Staphylococcus aureus. Most patients had polymicrobial isolates. Patients were followed up with clinical examinations, serial measurements of erythrocyte sedimentation rate, and scans using technetium Tc 99m medronate and gallium citrate Ga 67. Of the ten patients with chronic osteomyelitis who completed therapy, eight were considered cured. After further follow-up, three of the cured patients had recurrences requiring additional therapy.

Successful treatment of post-mitral valve annuloplasty Aspergillus flavus endocarditis.

Aspergillus endocarditis is associated with a very high mortality. Of approximately 67 cases reported in the English language literature, there have been only two known survivors. This report describes a patient with Aspergillus flavus endocarditis after mitral valve annuloplasty who recovered with combined surgical and antifungal therapy. This is the first successfully treated case due to A. flavus and the first involving an annuloplasty ring.

Recognition and treatment of adult respiratroy distress syndrome secondary to viral interstitial pneumonia.

Four cases of adult respiratory distress syndrome secondary to viral interstital pneumonia were treated successfully. The illnesses started with a prodrome of upper respiratory symptoms. The development of dyspnea was a key symptom from which point respiratory failure developed within 24 to 48 hours. Chest roentgenograms showed alveolar infiltrative patterns which later became coalescent. The clinical course consisted of fever, dyspnea, hypoxia and acidosis, There was no response to therapy with antibiotics, 100 per cent oxygen by mask and intermittent positive pressure breathing (IPPB) over the first 24 hours. Supportive therapy then initiated included endotracheal intubation, the administration of humidified oxygen by volume cycled respirator with positive end expiratory pressures of 10 to 15 cm H2O and corticosteroids. It is concluded that early recognition of the syndrome, coupled with prompt insituition of aggressive supportive respiratory management may be lifesaving in patints with severe interstitial pneumonia.

Correlation of antistaphylococcal antibody titers with severity of staphylococcal disease.

Counterimmunoelectrophoresis (CIE) was utilized to determine antistaphylococcal precipitin antibody titers in patients with various staphylococcal diseases and in control subjects. Patients with staphylococcal disease comprised five cases of endocarditis, 22 of deep tissue infection (including seven cases of osteomyelitis), six of bacteremia and six of skin infection. Control subjects consisted of 31 patients with nonstaphylococcal bacteremias, 29 hospitalized patients without infection and 30 healthy subjects. Antistaphylococcal antibodies were present in all patients with staphylococcal endocarditis and deep tissue staphylococcal infection, and all but three had titers greater than or equal to 1:4. No significant difference in titers was found between these two groups of patients. Antibodies, although present in some patients in the other categories, were detected less frequently; only two patients had titers greater than or equal to 1:4. Thus, an antistaphylococcal antibody titer by CIE of 1:4 or greater may be an additional diagnostic parameter helpful in distinguishing patients with staphylococcal endocarditis or deep tissue infection from those with other forms of staphylococcal infection and from noninfected subjects.

Effect of age on viral infections: possible role of interferon.

In both experimental animals and humans, three stages of susceptibility to viral infections are apparent: 1) the neonatal state, characterized by enhanced susceptibility to infections; 2) childhood and adolescence, during which there is decreased susceptibility; and 3) adulthood (sexual maturity), characterized by increased susceptibility to primary viral infections with advancing age. Moreover, advanced age is associated with reactivation of latent viruses, most notably VZV, and, most likely, oncogenic viruses as well. The mechanisms responsible for these alterations in susceptibility to viral infections have not been completely elucidated. Differences in antibody production do not seem to play a role. Most authors feel that depression of cell-mediated immunity, as measured by delayed cutaneous hypersensitivity or lymphocyte stimulation by mitogens and antigens may be of importance. There have been, however, only few studies on the role of antiviral moieties, such as the interferon(s). Our data on interferon formation in response to coxsackievirus B3 infection in mice suggest that adult mice produce relatively less interferon in relation to the amount of virus replicated in their tissues than do younger animals. Furthermore, the absolute amount of interferon produced by adult animals in response to intravenous injection of (non-replicating virus) NDV was less than that found in younger mice. We report our studies on interferon with no implication that these data supply an adequate explanation for the greater vulnerability of adult mice infected with coxsackievirus B3. It is unlikely that the matter of age and susceptibility has interferon (or indeed any other factor) as a single determinant.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial pneumonia in the elderly.

A retrospective study was made of patients having community-acquired pneumonia and treated at a large municipal hospital in 1973. Patients from nursing homes or other paramedical facilities were excluded. The incidence of Gram-negative bacillary pneumonia was significantly higher in elderly patients compared to two younger groups, and mortality from this type of pneumonia was higher than from pneumococcal or staphylococcal types or from pneumonia of unknown cause. Recommendations are made for the initial treatment of elderly patients with community-acquired pneumonia.

Detection of herpes simplex virus (HSV) type-1 IgG and IgM antibodies by enzyme-linked immunosorbent assay (ELISA).

A sensitive enzyme linked immunosorbent assay (ELISA) is described for detection of herpes simplex virus (HSV) type 1, IgG and IgM antibodies. The antigen consisted of a crude extract of HSV infected human foreskin fibroblast cells. Specific horseradish peroxidase conjugated antisera were used to detect total immunoglobulin, IgG and IgM antibodies bound to viral antigen. The substrate was a solution of 5-aminosalicylic acid and hydrogen peroxide, which yielded a readily visible endpoint. Results obtained by the ELISA method were compared with the micro-complement fixation (CF) method on 36 sera. ELISA was shown to be at least 10-20 fold more sensitive than CF, with a correlation coefficient of 0.752 (p less than .001). HSV antibodies in these sera were mainly IgG, although IgM antibodies could also be detected by ELISA. HSV antibodies were not found in 16 cerebrospinal fluids from patients without HSV encephalitis (HSVE). ELISA appears to be a rapid, sensitive, and specific method for demonstration of IgG and IgM HSV antibodies. It may have possible application in the diagnosis of HSVE.

Application of counterimmunoelectrophoresis in rapid detection of cytomegalovirus antibodies.

Determination of cytomegalovirus antibodies by counterimmune-electrophoresis correlated well with results of complement-fixation antibody studies. The sensitivity and specificity of the counterimmunoelectrophoresis method (vs. complement fixation) was 88.9%. Fourfold antibody increases detected by complement fixation were also detected by counterimmunoelectrophoresis. In addition, no cross-reaction was observed in the counterimmunoelectrophoresis assay between other DNA viral antisera and cytomegalovirus antigen (Ad-169).

Intra-abdominal abscess caused by Staphylococcus epidermidis.

An immunologically compromised patient was found to have a postoperative intra-abdominal abscess from which Staphylococcus epidermidis was the sole isolate. Studies of the isolate in a rabbit and in mice showed no evidence for unusual virulence of the organism. The S epidermidis probably was introduced into the peritoneal cavity during surgery and, because of the patient's neutropenia, produced a serious infection within a few weeks. To our knowledge, this is the first case of a intra-abdominal abscess associated with S epidermidis to be described in the literature.

Comparison of counterimmunoelectrophoresis (CIE) with other serologic tests in the detection of antibodies to Trypanosoma cruzi.

Application of counterimmunoelectrophoresis (CIE) in detection of antibodies against Trypanosoma cruzi in sera of 180 subjects from an endemic area (Bolivia), and 50 subjects from a nonendemic area (U.S.A.) was carried out, and the results were compared to ones obtained with latex agglutination (LA) and indirect hemagglutination (IHA). The optimal conditions for CIE were determined to be as follows: barbitone buffer of pH 8.2 and ionic strength 0.05 M was used in the chambers and in preparing the 1% agarose plates. The wells in the plates were 5 mm in diameter and 3 mm apart. Electric current was applied at 500 volts and 25 mA for 60 minutes. T. cruzi antigen (Center for Disease Control) was used in a dilution of 1:2. The sera were studied undiluted. The study population comprised the following groups: LA+ IHA+ (group I); LA+ IHA- (group II); LA- IHA+ (group III); LA- IHA- (group IV); and the control group (group V). Each group was comprised of 50 sera, except for group II which was comprised of only 30 sera. Antibodies were detected by CIE in 94% of sera in group I, 40% in group II, 76% in group III and 6% in group IV. There were no positive reactions in group V. CIE was positive in 74% of sera from the combined LA+ serum groups (I and II), and in 85% of sera from the IHA+ groups (I and III). A good correlation between CIE and the other tests in the LA+ and IHA+ group (I), and the lack of false positive reactions in group V suggest that CIE is a good diagnostic method for detection of T. cruzi antibodies. However, this study showed that IHA is a more sensitive test in epidemiological surveys than CIE. The finding of 6% sera positive by CIE in group IV may indicate a lower specificity of the test.

Antigen detection in the diagnosis and in the prognostic assessment of bacterial pneumonias.

Sputum cultures are not helpful in the immediate management of patients with bacterial pneumonia. Sputum Gram stains may provide a presumptive identification of an etiologic agent; this procedure, however, is insensitive (approximately 50%). Consequently, during the last decade, other more sensitive and specific methods of providing a rapid etiologic diagnosis have been sought. This article discusses data on antigen detection in various body fluids by counterimmunoelectrophoresis and agglutination tests. Results from our own laboratory as well as those reported in the literature are presented. The best estimates of antigen detection rates, by the most sensitive assays, in pneumococcal pneumonia, are as follows: serum, 45%-80%; urine, 50%-64%; and sputum, 75%-100%. There is less information for Haemophilus, Klebsiella, and Pseudomonas pneumonias, but the diagnostic yield is approximately 50%-100%. Data will also be presented on the association between free and complexed antigens and morbidity and mortality in pneumococcal pneumonia. Indicators of morbidity discussed include disseminated intravascular coagulation, duration and severity of illness, and occurrence of nephritis.

Recurrent herpes simplex labialis: viral replication and clinical course.

The purpose of this study was to provide additional information on the clinical course and viral replication kinetics of herpes simplex virus (HSV) in recurrent herpes labialis. Data were obtained on 20 subjects who were followed for five days from the first day of the lesion. HSV was isolated in 17 subjects (85%); 75% were positive on day 1 of the lesion. Median HSV titer on day 1 was 1.7 x 10(3)/0.2ml. Isolation rates and titers dropped sharply and virus could no longer be detected by day 4. The clinical course both in terms of the frequency and the severity of the symptoms paralleled the kinetics of viral replication. Thermography delineated location of subsequent lesions in three early symptomatic patients who were studied at the time when no visible lesions were observed. These data are felt to provide useful background information for future studies on the efficacy of topical antiviral agents.

Diagnosis and management of viral infections.

With the introduction of new diagnostic techniques and the expanding choices of antiviral agents, clinical virology is rapidly becoming an important field in infectious diseases. While effective therapy for several respiratory viruses, cytomegalovirus, hepatitis B virus, and Epstein-Barr virus is not currently available, herpes simplex, varicella zoster, and influenza A associated diseases can be adequately treated in many cases at the present time. New agents such as interferon, other nucleoside analogues, and immunomodulators are being investigated for their role in the treatment of viral illnesses, and many such illnesses with high morbidity and mortality may soon have effective therapy.