[Necrotizing vasculitis of the tongue. A contribution to the differential diagnosis of ulcerative mucosal changes in HIV-infected patients].
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Biomedical subjects
Publications and source records attributed to J von Overbeck.
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Sulfadiazine-nephropathy and -nephrolithiasis were well known complications of high dose sulfadiazine therapy 50 years ago. In the last few years high dose sulfadiazine therapy has been widely used for treatment of toxoplasmic encephalitis in AIDS patients. As a consequence sulfadiazine-nephropathy and -nephrolithiasis have become increasingly common. We describe 2 patients with the typical picture of these complications. Therapy is based on the fact that the solubility of sulfadiazine and its acetylated metabolite are markedly improved at higher urine-pH levels. Urine alkalinization is also effective for prophylaxis during sulfadiazine treatment. We present our guidelines for prophylaxis and treatment of these complications.
The differential diagnosis of recently acquired cough, diarrhea, headaches, odynophagia and fever in AIDS-Patients is discussed. The aim is to find the most frequent, the treatable and the most dangerous diseases. We discuss the empirical and the symptomatic treatment in special situations.
Systematic application of molecular techniques for epidemiology may serve as a useful tool in the evaluation of HIV transmission in small populations, and allows for better targeting of prevention programs while complementing classical epidemiological methods and preserving the privacy of individuals. Coded serum samples from 24 randomly chosen patients belonging to the HIV cohort of Berne were investigated by direct assessment of partial env gene sequences. This information was used to construct a preliminary sequence database. Thereafter, nine couples, amongst whom HIV transmission was thought possible, were assessed in a blind and coded fashion. Sequence data demonstrated that the main viral subtype circulating in Berne has the characteristics of the American-European HIV-1 strain (96% amino acid homology). 4 of 9 couples were shown to share viral strains. Other potential couples carried strains with sequence characteristics that did not support the possibility of transmission. These data provide a basis for future epidemiological studies in our community.
Disseminated nontuberculous mycobacteriosis is a frequent and late complication of HIV infection. All the 13 patients described here had CD4-lymphocyte counts < 20/mm3. The causative agent was mainly M. avium complex. But we also found, for the first time, a double infection with M. avium complex and M. "genavense" and one patient with growth of M. shimoidei in the blood culture. Clinical signs are nonspecific (fever, reduced performance, anemia). Positive cultures of blood or tissue biopsies are diagnostic. The therapeutic approach is the combination of new macrolides with other antimycobacterial agents. Prognosis is poor, mainly due to advanced immunodeficiency, but two of our patients survived more than one year after diagnosis. Prophylactic treatment should be considered in patients with CD4-counts less than 50/mm3.
OBJECTIVES: This paper describes the rationale and design features of the Swiss HIV Cohort Study (SHCS) and the baseline characteristics of participants enrolled up to March 31st 1993. The objectives include epidemiological, clinical and laboratory research. DESIGN: The SHCS is a prospective cohort study of HIV infected adolescents and adults seen at the outpatient clinics of the Swiss University Hospitals in Basle, Berne, Geneva, Lausanne and Zurich and the Cantonal Hospital St. Gall. The multicentre collaboration was initiated in September 1988 by the Swiss Federal Office of Public Health. Data collected prior to this date by several participating centers using a similar protocol were included, the earliest records dating back to 1982. Follow-up visits are scheduled every 6 months. ENROLLMENT: As of March 31st 1993, 6253 participants (M: 4580, F: 1675) were included with a total of 16015 person-years of follow-up (mean 2.6 years). HIV transmission categories were 46% intravenous drug users (IDU), 32% men who had sex with men (MSM), 18% heterosexual contacts (HET) and 4% other. The proportion of MSM among male participants decreased from 62% in 1985 to 40% in 1987, to remain stable thereafter. The proportion of IDU among males was around 40% throughout, whereas in females, there was a pronounced decline from 90% IDU in 1985 to 50% in 1992. Conversely, there was a striking increase in registrations of women presumably infected by HET, from 8% in 1985 to 50% in 1992. Among men, the proportion classified as HET increased from 2% to 15%. It is estimated, that a large proportion of all Swiss AIDS patients (70%) and HIV infected individuals (32%-47%) are enrolled in the Swiss HIV Cohort Study. Losses to follow-up, however, are common. CONCLUSIONS: The SHCS serves multiple purposes as a research project, as infrastructure for multidisciplinary research and as a tool to improve patient care. Several international and national trials, post-marketing surveillances and expanded access protocols were or still are based upon its infrastructure. The large number of female participants and of participants AIDS-free at entry, make the database especially valuable.
OBJECTIVE: To examine survival differences in HIV-infected individuals between the sexes and the categories of transmission. PATIENTS AND SETTING: Subjects assumed to have been infected by injecting drug use, by male homosexual contact or by heterosexual contact and enrolled in the Swiss HIV Cohort Study, a national multicentre cohort study of adult HIV-infected patients. METHODS: Kaplan-Meier lifetable and Cox regression analyses were performed (time 0 = date of study entry) and survivors were censored at their last follow-up visit. RESULTS: A total of 4428 patients (mean duration of follow-up, 2.1 years) were considered. At entry, men were older and had lower CD4+ counts than women (P < 0.0001). Homosexual men were the oldest group with the lowest CD4+ counts and the most advanced disease at study entry (P < 0.0001). Crude hazard ratios indicated a 28% lower mortality from all causes in women compared with men (P < 0.0001) and, among men but not in women, a 28 and 32% higher mortality in homosexuals and heterosexuals compared with injecting drug users (IDU) (P = 0.0002 and P = 0.008, respectively). After adjusting for differences at entry, the mortality difference between the sexes disappeared (P = 0.5) and differences across transmission categories were reversed. Mortality in homosexual men was an estimated 13% (P = 0.057) lower than in male IDU; mortality was 22% lower in heterosexual women than in female IDU (P = 0.098). In stratified analysis the increased risk in IDU was confined to subjects with CD4+ cell counts > 500 x 10(6)/l cells at study entry. CONCLUSIONS: These results indicate a uniform mortality risk across the sexes but indicate an increased risk in IDU without CD4+ cell depletion at entry, the latter probably attributable to causes not related to progression of HIV infection. This study underscores the importance of adjusting for prognostic factors when comparing survival between different patient groups.
In order to elucidate mucosal immunity in HIV-1 seropositive individuals, we investigated oral mucosa washings from 20 HIV-1 seropositive patients for the presence of Langerhans cells (LC) and HIV-1 antigen-positive cells, and compared the results with those obtained from 20 HIV-1 seronegative healthy individuals. Monoclonal antibodies directed against CD1a, HLA-DR, CD3, and p24 were used to identify LC, T cells and HIV-1 core-antigens, respectively. In oral mucosa washings from HIV-1 seropositive patients there was a significant reduction in the number of CD1a+ cells as compared with the healthy subjects. HIV-1 antigen-positive cells were not detected. The reduction of LC in oral mucosa washings from HIV-1 seropositive patients is probably associated with HIV-1 infection. The frequent occurrence of oral mucosal disorders in HIV-1 infected patients may in part be caused by a reduced LC-number and/or function.
Candida sepsis in surgical patients is rare, but accounting for a high lethality. The diagnosis of a candidemia is based by most authors upon two positive blood cultures in 24 h or on proof of fungi in an organ parenchyma or a normally sterile body cavity. The risk factors for the development of a candida sepsis are administration of broad spectrum antibiotics, invasive monitoring, underlying diseases affecting the immune response and surgery itself. We have checked the charts of 22,740 patients of our clinic from 1987-1992. We found 11 patients (6 male, 5 female) with a mean age of 53.2 (34-76) years with a candida sepsis. The known risk factors for the development of a candida sepsis could be confirmed: broad spectrum antibiotics 100%, invasive monitoring 100%, condition after operation 64%, nasogastric tube 54%, condition after endoscopy 45%, steroid medication 36%. Lethality was 27% (3/11); two out of three patients with a multiple organ system failure died. Recently, it has been shown that mortality was associated with older age and concomitant multiple organ system failure. The treatment of choice for fungal sepsis is intravenous amphotericin B. Finally therapeutic guidelines, the indication for a selective bowel decontamination and the question of prophylaxis with antifungal agents in all postoperative patients are discussed.
Cervical adenopathy is often found on examination, but rarely causes clinical problems. If the adenopathy persists for a longer period then three to four weeks and no infectious causes are found, further investigations are needed, especially to exclude a malignancy. The chronic infectious adenopathies are discussed: mycobacterial (tuberculous and atypical), toxoplasmosis, cat-scratch disease and actinomycosis.
Accidental exposure to blood carries with it a definite risk for the health care worker of infection by various bloodborne pathogens, especially the hepatitis B, hepatitis C, and human immunodeficiency virus. The risk of transmission from exposure to HIV is lower than that associated with exposure to HBV and HCV. Should HIV infection occur, however, the outcome is likely to be fatal. Although general infection control precautions, safer use of needles, gloves, and other procedures may substantially reduce the incidence of occupational exposures, they cannot eliminate the risk completely. The post-exposure management is discussed. Neither the efficacy nor the safety of AZT (zidovudine) for use as a chemoprophylactic agent following occupational exposures to HIV has been established. Nevertheless in selected cases it can be proposed to health care workers.
Traveller's diarrhea is a common problem without consequences for a healthy patient. Correct information, especially about hygiene habits during the trip, is most important. The prescription of an anti-diarrheal medication is usually justified but should not be given without proper information about the possible dangers. A prophylactic antibiotherapy is very seldom necessary. Antibiotic self-medication can be a pragmatic alternative. Patients at risk must be identified before the trip, and appropriate measures are essential. Once the patient is back home again diarrhea will subside spontaneously and both patient and physician should therefore know to be patient.
A mouse monoclonal antibody, MAb b-12, has been described previously (Stähli et al. 1985) which reacts with a Mr 350 kD glycoprotein with mucin-like characteristics (Stähli et al. 1987) expressed in cytoplasm and on the surface of human breast carcinoma cell lines (MCF-7 and ZR-75-1). In the present report the immunohistochemical reactivity of this MAb with normal and malignant human tissues is analyzed. Pre-experiments showed that the epitope b-12 is resistant to formalin treatment allowing the use of tissue processed by standard paraffin embedding methods. 167 normal and 408 neoplastic tissues were tested by indirect immunofluorescence or the avidin-biotin complex method. MAb b-12 stained the apical cytoplasm of secretory epithelia and their secretions including the acinar and ductular epithelia of the breast. It reacted with all breast carcinomas independent of their histological type or stage, frequently with all but in some cases with a fraction of the tumour cells. Some other carcinomas, primarily those of adenomatous differentiation, were also reactive. In these, however, the fraction of positive tumour cells was usually lower. The b-12 epitope is thus a marker for normal and neoplastic epithelia with secretory functions, particularly for breast carcinomas of all histological types and stages, and perhaps a differentiation marker for abortive adenomatous differentiation in solid carcinomas of the gastro-intestinal, uro-genital or respiratory tract.
The epitope recognized by the murine monoclonal antibody (mAB lu-5) recently described as a formaldehyde-resistant, "pan-epithelial marker" of great value in tumour diagnosis is located on the surface of cytokeratin filaments. It has been preserved during vertebrate evolution from amphibia to man. As this epitope is not reactive after SDS-polyacrylamide gel electrophoresis (SDS-PAGE), the epitope-bearing protein has been identified by a dot-blot antibody binding assay, using purified proteins in which the epitope is reconstituted. We show that the epitope is present in most cytokeratin polypeptides of both the acidic (type I) and basic (type II) subfamily but does not occur in other cytoskeletal proteins. The location of this widespread epitope is discussed with respect to homologies of amino acid sequences of cytokeratins and their conformations.
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A systematic study of an autofluorescence method is described to improve the early histological diagnosis of myocardial ischaemia. Our results on 732 autopsy cases including 182 cases of sudden death show that the autofluorescence examination of haematoxylin and eosin stained sections of the myocardium is not only reliable in the identification of recent ischaemic lesions, but contributes to a better histological evaluation. In 24 cases undetected by white light examination it allowed recognition of ischaemic lesions.
The method described below combines an immunoreaction with Papanicolaou's stain on cytological smears. For the immunoreaction, the avidin-biotin-complex (ABC) method was used. The method was tested on various cytological material with the monoclonal antibody lu-5 and two polyclonal antibodies (anti-keratin and anti-chymotrypsin). Wet fixation of the smears with a modified Delaunay's solution is recommended. Drying of the material impairs immunoreactivity. The main advantages of the technique are the clear-cut permanent immunostaining and the preservation of the nuclear structure, permitting a combined immuncytological characterization of cellular products and conventional cyto-diagnosis.
A mouse monoclonal antibody (mAB lu-5) was prepared using a lung cancer cell line as an antigen. The selected clone produces an IgG with a gamma-1 heavy chain and a kappa-light-chain. Immunohistochemical testing of mAB lu-5 on 117 normal tissue biopsies and 474 tumours revealed reactivity with an intracytoplasmic, formaldehyderesistant antigen present in most epithelial and mesothelial cells, but absent in mesenchymal cells. The antibody can therefore be used as a first order, pan-epithelial marker. It proved also useful for fast tumour diagnosis on frozen sections.