Michael W. Rytel

Possible pathogenetic role of capsular antigens in fulminant pneumococcal disease with disseminated intravascular coagulation (DIC)

Abstract The mechanism(s) responsible for initiating disseminated intravascular coagulation (DIC) in patients with pneumococcal sepsis are unknown. Two fatal cases (one of which was asplenic) of fulminant pneumococcal disease and DIC were studied for the presence and amount of circulating capsular type-specific antigens. The amounts found were larger than those detected to date in other cases of pneumococcal antigenemia in which DIC did not develop. In addition, C3 and C4 were depressed in both patients, and in one, focal membranous glomerulitis was present, compatible with that seen in antigen-antibody complex disease. Pneumococcal antigen, immunoglobulins and complement (C3) were identified on the basement membrane. It is proposed that pneumococcal capsular polysaccharide antigens initiate the DIC either directly, or as part of an antigen-antibody complex, by activation of complement.

Pneumococcal Vaccine Immunization of Patients with Renal Impairment

Abstract The immunogenicity of the polyvalent pneumococcal vaccine was studied in renal allograft recipients and dialysis patients. There was no significant overall difference in the antibody response of the allograft recipients compared to control subjects at 1 month following immunization. Chronic hemodialysis patients had significantly lower postvaccination antibody levels for 6 of 12 serotypes. Better graft function in the allograft recipients correlated positively with higher antibody levels. Azathioprine and prednisone in dosages employed had no consistent effect on antibody response. No deterioration of renal function ascribable to the vaccine was observed. Patients were sampled at 1,2, and 3 1/2 years following immunization. Geometric mean titers (GMT) were calculated for all the serotypes per group for each time of sampling. There was a significant decrease with time in antibody GMTs for all the groups (P < 0.01). Chronic hemodialysis patients had significantly lower GMTs than control subjects and allograft recipients at 1, 2, and 3 1/2 years postimmunization (P < 0.05). The 3 1/2 years postimmunization antibody levels were very low in dialysis patients, suggesting that reimmunization of these patients may be required.

Therapy of cytomegalovirus retinitis with transfer factor

Abstract A renal transplant recipient who was rapidly losing his vision due to cytomegalovirus (CMV) retinitis was treated with transfer factor (TF). TF was prepared from lymphocytes of a subject with CMV mononucleosis who had cell-mediated immunity to CMV as assayed by lymphocyte transformation ([ 3 H] thymidine uptake) and migration inhibitory factor (MIF) production. Within 2 mo of initiation of TF therapy, all of the patients foci of retinal inflammation became inactive. This was his second episode of acute retinitis within 4 yr. The first one required reduction in the dose of immunosuppressants to achieve remission, whereas during the present exacerbation, immunosuppressants were maintained at a pre-TF therapy dosage. It is of interest that immediately after initiation of TF, a previously quiescent area of retinitis became inflamed; however, after several additional doses of TF, this reactivation subsided. In addition, the patient developed (though transiently) a positive delayed skin test to one of the antigens (SK-SD) to which the donor of the TF was sensitive, and although lymphocyte transformation by CMV antigen remained negative, there was evidence of MIF production. Finally, the patients urine CMV titer declined from persistently high titers of 10 3.5 to 10 4.5 TCID 50 to a titer of 10 0.5 TCID 50 , which was the lowest observed during the 4 yr of study. We conclude that it is unlikely that these findings were due to chance. TF should receive wider clinical trials in certain viral infections, particularly in immunosuppressed hosts.

Assessment of the status of cell-mediated immunity in cytomegalovirus-infected renal allograft recipients.

Abstract Renal allograft recipients are unusually susceptible to cytomegalovirus (CMV) infections. Since humoral immunity to CMV is uncompromised in these patients, it was felt desirable to assess the competence of cell mediated immunity (CMI). Several parameters were used. On skin testing with candida, SK-SD, mumps, and PPD-5 antigens, 80.0% of patients and 5.0% of controls were unreactive. T-lymphocyte ratios (SRBC rosette test) were 18.7% in transplant patients, vs. 40.3% in controls. These differences are statistically significant. Lymphocyte stimulation assay ([ 3 H] thymidine uptake) was developed to study CMI to CMV. Lymphocytes from all the normal seropositive subjects (10) had increased [ 3 H]thymidine uptake on exposure to CMV antigens. There was no antigen specific stimulation of lymphocytes from the seronegative controls (five). Six of nine (67.7%) CMV infected renal allograft recipients, studied six or more months post-transplantation, had no evidence of CMI to CMV by this assay.

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.

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.

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)

Counterimmunoelectrophoresis in the Detection of Antibodies Against Coccidioides immitis

In recent years counterimmunoelectrophoresis has been increasingly used in the diagnosis of microbial diseases, and our study was undertaken to evaluate its possible use in the rapid detection of antibodies against Coccidioides immitis. One hundred twelve specimens from 50 patients were studied. The study population comprised the following: Group I, 34 patients with an active coccidioidomycosis infection; Group II, five patients with a positive coccidioidin skin test; Group III, five patients with a negative coccidioidin skin test; and Group IV, six patients with other fungal infections. Counterimmunoelectrophoresis was positive in 93 of 96 specimens in Group I and negative in the other groups. The results obtained by counterimmunoelectrophoresis correlated well with complement fixation and double immunodiffusion and indicate that it is an excellent tool for the diagnosis of patients with coccidioidomycosis.

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 × 103/0.2 ml. 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.

TRANSFER FACTOR TREATMENT OF VIRAL DISEASES IN MILWAUKEE

Publisher Summary This chapter describes the transfer factor (TF) treatment of viral diseases in Milwaukee. Transfer factor therapy has been used for treatment of seventeen patients with a variety of disorders known, or suspected to involve virus infection. Nine patients have experienced clinical improvement. After receiving two injections, 0.05 units each, the patient reported improvement in his upper limb arthritis and developed numerous pustular eruptions in his scalp and on his upper arms. After a three week interval of not receiving TF, the patient returned with arthritis. Administration of 0.1 unit of TF each week for 7 weeks was accompanied by gradual improvement of the arthritis, all genital ulcers had healed, but oral ulcers persisted. The patient reported that injection of TF the affected joints were very painful for about 2k hours. TF from a new donor was instituted while the patient was free of arthritis, and had only one small oral ulcer.