[Education of the internist: a methodical approach is indispensable].
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Biomedical subjects
Publications and source records attributed to H Stalder.
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A phase 1 trial of a candidate human immunodeficiency virus type 1 (HIV-1) vaccine was done in 25 healthy seronegative subjects. The antigen, env2-3 (SF2), was a nonglycosylated polypeptide representing the gp120 region of the env gene of the HIV-1(SF2) isolate. It was produced in genetically engineered yeast as a denatured molecule incapable of binding CD4. A synthetic lipophilic muramyl tripeptide (MTP-PE) was used as an adjuvant. Ten subjects received adjuvant alone and 15 received 50- or 250-micrograms doses of env2-3 (SF2) administered intramuscularly in two immunization regimens. In general, adjuvant and vaccine were well tolerated. Antibody responses to both the homologous antigen, env2-3 (SF2), and antigens from other highly divergent HIV isolates were elicited in the majority of vaccine recipients. However, antibody titers were low, without neutralizing activity. In 9 of 11 subjects who received the complete vaccine immunization series, a significant specific T lymphocyte response was observed.
Reported here is a case of hereditary myeloperoxidase deficinecy in a diabetic patient suffering from a Candida albicans liver abscess. Peroxidase activity is completely absent from the neutrophils and monocytes although it is present in the eosinophils. The different forms of myeloperoxidase deficiency are discussed.
Indirect hemagglutinating and immunofluorescent antibody responses to Herpesvirus hominis types 1 and 2 were compared to neutralizing antibody responses in infected humans from whom H. hominis type 1 or 2 was isolated. The indirect immunofluorescent antibody test was shown to be the most sensitive and specific for primary human infections. The sensitivity and specificity of the indirect hemagglutination and the immunofluorescent antibody tests were shown to be equal to that of the microneutralization test among patients who had primary or recurrent H. hominis type 2 infections. It is suggested that the indirect hemagglutination test is preferable for assaying large populations for previous infection with H. hominis type 2 because it is rapid, easier to perform, and more economical. The intermediate range of titer differences (deltat) between H. hominis types 1 and 2 previously reported to be due to infections with both viruses was shown to occur in all three tests among patients with primary infections with either virus.
To determine the cellular site for uptake and degradation of circulating prostaglandins (PGs) by the lung, the metabolism of PGA1 and PGF2 alpha was studied in pig lung slices, smooth muscle preparations, and pulmonary valves, as well as in isolated and cultured endothelial cells and cultured fibroblasts. Formation of 15-keto metabolites of both PGA1 and PGF2 alpha by lung slices was confirmed. No evidence of PGF2 alpha degradation could be found in any of the remaining preparations. For PGA1, however, 15-hydroxyprostaglandin dehydrogenase activity was detected in the three smooth muscle preparations studied (trachea, aorta, pulmonary artery) and found to be similar to that measured in lung slices. But the inhibitory effect of diphloretin phosphate and bromcresol green was much more marked in smooth muscle tissues than in lung slices, which suggested that PGA1 metabolism by the lung was not due to smooth muscle cells. Endothelial cells, freshly isolated and cultured, originating from the pulmonary artery and from the aorta, formed a PGA1-glutathione adduct, poorly extractable in ethyl acetate. This reaction, also present in cultured fibroblasts, was inhibited by ethacrynic acid. The cellular site responsible for the pulmonary degradation of circulating PGs remains undetermined.
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Echocardiographic demonstration of vegetations has been achieved in 11 out of 19 patients with bacterial endocarditis. The present study shows that echocardiography is particularly useful in patients in whom the duration of symptoms before treatment is greater than 6 weeks. It also shows that a positive echocardiogram is indicative of a poor prognosis.
A case is reported of hereditary myeloperoxidase deficiency in a diabetic patient suffering from a Candida albicans hepatic abscess. Myeloperoxidase (MPO) is completely absent from the neutrophils and monocytes, although it is present in the eosinophils. Functional granulocyte studies have revealed normalchemotactic and phagocytic activity, although the bacterial activity is partially diminished with regard to Staphylococcus aureus and is almost nil with regard to Candida albicans. The granulocytic metabolism, when stimulated by zymosan, is characterized by greatly increased oxygen consumption. Genetic investigations have been conducted in 28 members of the patient's family. Cyto- and biochemical determination of MPO is clearly diminished in close relatives of the patient. Genetic analysis indicates recessive autosomal transmission with variable expressivity of the gene for the heterozygote state.
An antigenically distinct adenovirus is described which was isolated in March 1973 from the lungs and kidney of a 61-year-old woman who died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. Complement fixation, hemagglutination inhibition, and serum neutralization tests on sequential serum specimens from the patient confirmed that the adenovirus infection occurred in coincidence with her clinical illness and failed to document concomitant infection by any other common respiratory agent. Pathological and virological findings indicated that the pneumonia was only one manifestation of a disseminated adenovirus infection, the source of which may have been a latent infection pre-existing in the donor kidney. The adenovirus, purified by terminal dilution and plaque procedures, has antigenic, morphological, biological, biophysical, host susceptibility, and hemagglutinating properties characteristic of adenovirus group 1A. Buoyant densities in CsCl are 1.340 g/ml for the virion, 1,300 g/ml for the group complement-fixing (hexon) antigen, and 1.290 g/ml for the major soluble complete hemagglutinin (dodecon). The virus was serologically distinct from adenoviruses 1 to 34 in reciprocal serum neutralization tests with antisera to these viruses. We propose this virus as candidate adenovirus type 35 (holden).
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A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.
The herpes simplex virus (HSV) microneutralization test has been simplified; its use has been demonstrated for the identification of HSV isolates as type 1 (HSV-1) or type 2 (HSV-2) and for the measurement of antibodies to HSV-1 and HSV-2. In this test, the relation between the neutralization titer and virus input is linear, and thus test results can be expressed as corrected neutralization titers, rather than as the more complex neutralizing potency values previously proposed. By means of this test, 45 of 46 clinical isolates of HSV were unequivocally identified as either HSV-1 or HSV-2. Evaluation of neutralizing antibody to HSV infection was more difficult because some neutralizing antibody to the heterotypic HSV is produced after primary infection with HSV-1 or HSV-2, because patients previously infected with one HSV type may show a variety of serological responses to subsequent heterotypic infection, and because human sera obtained early after primary HSV infection may not yet exhibit a type-specific response.
The current status of antiviral therapy is reviewed, including discussion of older approaches together with more recently developed chemotherapy. Following the introduction dealing with pathophysiological aspects of virus disease, the different approaches to antiviral therapy are presented. The reasons for the slow progress in antiviral therapy are discussed. These include: 1. the necessity of intracellular penetration of drugs acting on viral replication; 2. the severe toxicity of most antiviral drugs; 3. the narrow antiviral spectrum of most of these agents; 4. the difficulty of making a rapid etiological diagnosis in view of the necessity of starting (specific?) treatment early in the course of the disease; 5. the difficult evaluation of beneficial as compared with deleterious effects of antiviral therapy. After a detailed review of clinically tested substances, including immunoglobulins, synthetic antiviral drugs (amantadine, nucleoside analogs, thiosemicarbazones and photodynamic dyes) and interferon, a guide concerning indications and application of specific antiviral therapy is presented. Although at present there are few indications, clinicians should be aware of the (present and future) possibilities of antiviral therapy.