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Biomedical subjects

E M Fabricius

Publications and source records attributed to E M Fabricius.

At least 19 recordsLinked to original sources

Immunohistochemical assessment of the tumour-associated epitopes CD44v6 and E48 in tumour-free lymph nodes from patients with squamous cell carcinoma in the head-neck region.

We examined immunohistochemically 370 tumour-free lymph nodes from 41 patients with a head and neck squamous cell carcinoma (HNSCC) to clarify whether the tumour-associated epitopes CD44v6 and E48 are suitable for adjuvant postoperative immunotherapy. All the positively immunostained cells found were single cells. CD44v6+ cells were found in 55% of the lymph nodes, with their numbers increasing in pN>0-patients (62%). Only pN>0-patients had abundant to massive CD44v6+ cells. A comparison with mononuclear cells in lymphatic tissue from control patients suggested a similarity with activated T-cells. In the 41 cancer patients there were significantly fewer lymph nodes with E48+ cells (11%), but the number of E48+ cells increased in pN> 1-patients (29%) with predominantly abundant E48+ cells. We conclude from the comparison with the epithelial marker EMA that the E48+ single cells are epithelial in origin. Only a specific E48 peptide sequence appears suitable for adjuvant immunotherapy in patients with head-neck tumours.

Aged↗

Different expression of the alpha2-macroglobulin receptor/low-density lipoprotein receptor-related protein in human keratinocytes and fibroblasts.

We compared, using a combination of different immunological methods and by competitive PCR, the expression of the alpha2-macroglobulin receptor/low-density lipoprotein receptor-related protein (alpha2-M-R/LRP) in human keratinocytes and fibroblasts. This receptor has previously been found in skin only in dermal cells associated with fibroblasts and dendritic cells. For immunodetection we used mouse monoclonal antibodies against the two subunits of the receptor and against the receptor-associated protein (RAP), known as the regulatory protein of the receptor activity. The alpha2-M-R/LRP was found to be predominantly located intracellularly in keratinocytes whereas a distinct labelling of the outer membrane surface was found in fibroblasts. RAP is abundant in fibroblasts but is less expressed in keratinocytes. In frozen skin sections receptor immunoreactivity was detected in the epidermis with increased reactivity of basal keratinocytes, as well as in the dermis in association with dermal fibroblasts. By immunoprecipitation of biotinylated cell extracts, polypeptides were identified corresponding to the alpha-subunit and beta-subunit of the receptor as well as to the coprecipitating RAP. Competitive PCR revealed the presence of 67.9 and 2049.7 ag of alpha2-M-R/LRP mRNA per cell in keratinocytes and fibroblasts, respectively. The results demonstrate that both cell types express alpha-M-R/LRP mRNA and contain receptor protein as well as RAP but in different quantities and subcellular localizations.

Animals↗

[Why are AIDS patients frequently visually impaired?].

Patients with HIV infection and, above all, patients with full-blown AIDS can get a variety of ocular diseases as well as some cerebral maladies which have an influence on ocular functions. First there are hematogenous opportunistic infections of the retina or the choroid. The cytomegalovirus [CMV] retinitis was found in nearly 20% of all AIDS patients. Without treatment this disease destroys the retina completely, and the involved eye becomes blind. This can be prevented by modern therapeutic strategies in most of the cases. Other infections affecting the retina are toxoplasmosis, systemic varizella zoster or herpes simplex virus infections, syphilis or, seldom, fungal or bacterial pathogens. The choroid mainly can be infested by mycobacteria, cryptococci and pneumocystis carinii. Early detection and treatment of all inflammations are necessary. The anterior eye can be affected by a sicca syndrome and various superficial infections but also noninfectious inflammation. The anterior uvea can be involved in various opportunistic infections of the posterior eye segment. An HIV-associated isolated anterior uveitis has been described in earlier stages of the HIV infection. Treatment of mycobacterial infections with rifabutin can cause an anterior uveitis as well. 1 to 2% of HIV-infected persons suffer from a zoster ophthalmicus with more severe keratitis than it occurs in immunocompetent persons. Last but not least, there are various cerebral affections which can cause visual disturbances. So the optic nerve can be involved in various forms of retinitic or meningoencephalitic processes, of ischemic mechanisms or elevated intracranial pressure. Neuroophthalmological symptoms also include homonymous hemianopsia caused by foci of cerebral toxoplasmosis, progressive multifocal leucencephalopathy or primary intracerebral malignant lymphoma situated in the central neuron of the afferent visual pathway. A variety of oculomotor abnormalities can be caused by a great variety of cerebral disease. Moreover, there are signs of neuroretinal dysfunction in computed perimetry and in color vision or contrast sensitivity testing. Some sight threatening diseases initially can be symptomless for the patient, though they should be treated immediately in order to keep the remaining visual damage small. Thus, regular ophthalmological investigations are necessary in patients with an advanced stage of the immunodeficiency, regardless whether they have ocular complaints or not. Moreover, the patients have to be advised to attend an ophthalmologist immediately, when they notice any kind of visual disturbances or ocular symptoms.

AIDS-Related Opportunistic Infections↗

[Epidemiology of HIV infection].

HIV-infected people are infectious during the 10-20 years' incubation time as well as while suffering from AIDS. The disaster of this lentivirus epidemic is that there is a long time interval between source (virus inoculation) and result (manifestation of AIDS). The registered AIDS cases represent only the tip of a mountain. By now, more than half of a million AIDS cases are reported to the WHO, but the real number is assumed to be double. In Europe about 80,000 AIDS patients are registered. In most of the industrialized countries where now a certain stagnation among the typical risk groups of homosexuals and drug addicts is visible, now one can see a slow, steady increase among the heterosexual population. In Europe at this time 18% of the newly diagnosed AIDS cases are women. The number of HIV-infected persons reflects the number of AIDS patients to be expected for the next years. In Germany 1 per thousand of the population are infected (55,000-90,000 persons), in Switzerland 2-4 per thousand (20,000-30,000 persons). Worldwide 12-13 millions of people are estimated to be HIV-infected, and projections for the year 2000 expect 38-110 millions. More than 50% of AIDS patients have ocular manifestations.

AIDS-Related Opportunistic Infections↗

[Cytomegalovirus retinitis in AIDS. Effectiveness and complications of long-term therapy].

In a retrospective study of the records of 64 patients with AIDS and cytomegalovirus (CMV) retinitis, 47 patients were evaluated regarding the effectiveness of initial virustatic therapy, and 41 patients regarding the anatomical and functional long-term development (maintenance therapy, rate and intervals of recurrences, complications, adverse drug reactions, time of survival, and visual outcome). The average survival time of 45 treated patients was 226 days (31-717 days). More than 90% responded to initial therapy with ganciclovir or foscarnet. Forty-four percent remained free of recurrences until they died (for up to 15 months); 56% had 1 to 4 recurrences, altogether 35 episodes, of which 14 occurred after withdrawal of therapy. Recurrences were treated with high-dose reinduction therapy with good or partial response in more than 80% of cases. Nine patients showed "smouldering retinitis" at a late stage. Two out of 45 patients became blind shortly after diagnosis despite therapy; both showed a course mimicking acute retinal necrosis syndrome with histologically proven CMV disease. None of the 43 patients on maintenance therapy for up to 2 years became blind in both eyes. Only 2 out of 43 patients had a poor visual outcome < 40/100 in the better eye at a late disease stage. Of 60 affected eyes, 11 showed retinal detachment, 14 eyes developed optic atrophy and 12 eyes became blind. Our retrospective study shows that consistent maintenance therapy of patients with CMV retinitis prevents severe deterioration of visual acuity in most cases even in long disease courses and thus maintains quality of life.

AIDS-Related Opportunistic Infections↗

Ocular myositis as first presenting symptom of human immunodeficiency virus (HIV-1) infection and its response to high-dose cortisone treatment.

A 30-year-old male presented with signs of ocular inflammation and motility disturbances in an early stage of HIV infection. The provisional diagnosis of an ocular myositis was confirmed by orbital echograms. A general check up revealed positive anti-smooth-muscle antibodies and antinuclear antibodies as well as a raised erythrocyte sedimentation rate. Oral steroid treatment in addition to steroid eyedrops achieved complete resolution of clinical and sonographic symptoms within 15 weeks. Autoimmune phenomena are well known presentations of HIV infection. In this case oral cortisone proved to be an effective therapy even in the setting of an HIV infection.

Acquired Immunodeficiency Syndrome↗

[Prevalence, morphology and therapy of toxoplasmosis chorioretinitis in AIDS].

Toxoplasmosis-retinochorioiditis is the second most frequent opportunistic infection of the eye among our series of AIDS patients. Between 1985 and 1990 we diagnosed 7 cases in 261 AIDS patients (Walter Reed classification 6); prevalence = 2.7%). The incidence has been increasing over the years. In four cases, toxoplasmosis was restricted to the eye, in three cases, ocular disease occurred combined with toxoplasmosis of the central nervous system. Since serological findings are not very reliable in AIDS-patients, the most important element in the differential diagnosis against retinitis of different etiology is ophthalmoscopy. There are a number of findings which allow differentiation of toxoplasmosis from other forms of retinitis, especially cytomegalovirus retinitis. Toxoplasmosis-retinitis was stopped in all cases by administering a specific therapy of pyrimethamine combined with clindamycin, a sulfonamide or spiramycin. Stable scar formation was achieved after 2-3 weeks therapy. Subsequent maintenance therapy with Fansidar (pyrimethamine + sulfadoxine) protected 4/4 patients from a relapse, while maintenance therapy with pyrimethamine alone allowed a relapse in 1/2 patients.

Acquired Immunodeficiency Syndrome↗

[Acute retinal necrosis and HIV infection].

Acute retinal necrosis (ARN) is increasingly being observed among patients with HIV infection. Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are recognized as being the etiologic agents in this syndrome. Among the 538 patients with HIV infection (261 of these with AIDS), who were followed up in our department between 1985 and 1990, we diagnosed ARN in 4 cases. Three of these patients suffered from AIDS. Thus, ARN was the third-most-frequent form of retinitis in our patients with AIDS (prevalence 1.1%), following Cytomegalovirus (CMV) retinitis (17.2%) and toxoplasmosis-retinochorioiditis (2.7%). The course of ARN in patients with AIDS is demonstrated in four case reports. Special features of the retina are documented by photographs of the fundus. The authors suggest that patients with AIDS who experienced an episode of VZV- or HSV infection which necessitated high-dose systemic aciclovir therapy are at risk of developing ARN. We recommend that they be kept on virustatic maintenance therapy.

Acyclovir↗

[Disorders of the afferent visual pathway in HIV infection. 1. Optic nerve and 2. Visual pathways/visual cortex].

Up to now little involvement of the afferent visual pathway (optic nerve and optic radiation and visual cortex) in HIV infection has been apparent. These results are based on our prospective investigations of 538 HIV-infected individuals, among them 261 patients with full-blown AIDS carried out by the same examiner over a 6-year period (1984-1990). Diseases of the optic nerve were observed in 22/261 (8.4%) of Aids patients but in only 1/227 (0.4%) of patients with earlier stages of HIV infection. Optic neuritis was the most common disease (in 14/261 = 5.4% of Aids patients), for the most part occurring in the course of CMV (cytomegalovirus) retinitis. For this form the prognosis was primarily good under virustatic therapy with ganciclovir in contrast to primary CMC papillitis. Furthermore, a few cases of optic perineuritis, optic neuropathy in basal meningitis, ischemic optic neuropathy and papilloedema with increased intracranial pressure were observed, most of them caused by opportunistic infections of the central nervous system. In single cases the HIV might hypothetically have played a role in the etiology. Visual impairment of the patients varied from subtle disturbances to blindness. Often optic atrophy resulted. Homonymous hemianopsia was the principal sign in diseases of the visual pathway between the lateral geniculate body and the visual cortex (in 10/261 = 3.8% of Aids patients). This symptom resulted from cerebral toxoplasmosis in 7 cases, progressive multifocal leukoencepalopathy (PML) in 2 cases and primary intracerebral malignant lymphoma in 1 case. The visual fields and neuroradiological findings are demonstrated. In 3 cases the homonymous hemianopsia was the first clinical appearance of Aids. Involvement of the afferent visual pathway in HIV infection may be a cause of blindness or visual disturbances despite normal findings on examination of the eyes themselves.

Fluorescein Angiography↗

[Acute retinal necrosis and herpes encephalitis. The key role of the ophthalmologist in diagnosing opportunistic infections in AIDS, successful therapy with acyclovir (Zovirax)].

A 43-year-old homosexual man was hospitalized in April 1988 because of acute epigastric pain. It was known that he had had a HIV infection for a year, and in April 1988 it was defined as stage Walter Reed I. Acute, exudative, nonspecific pancreatitis was diagnosed. Three weeks later cerebral symptoms (disturbances of consciousness), hypoacusis, and impaired vision developed. The ocular fundus displayed areas of edema and whitish clouding in the retina, first in the left eye and later also in the right. These were initially assumed to be anemic infarctions until the differential diagnosis of acute retinal necrosis with possible herpesvirus infection was made. On the basis of ophthalmoscopic findings cytomegalovirus retinitis appeared improbable. Serologic examinations showed increased levels of IgG antibody titers of cytomegalovirus and herpes simplex virus (both 1:20,000). Therapy with intravenous infusions of Acyclovir was instituted (1500 mg/d). After a few days the patient regained consciousness as well as his hearing and vision. There was complete resolution of the retinal exudates. This excellent therapeutic result of Acyclovir therapy confirmed the diagnosis of acute retinal necrosis syndrome, identified the cerebral symptoms as herpes encephalitis, and explained the entire disease process as the first opportunistic infection in HIV infection, i.e., by that time the patient had developed stage Walter Reed 6 (AIDS). Problems of differential diagnosis and the therapeutic schedule with Acyclovir are discussed.

Acquired Immunodeficiency Syndrome↗

Application of microbiological cancer test to cattle infected with bovine leucosis virus.

A microbiological cancer test, previously verified in men and dogs using a clostridium strain (Clostridium butyricum CNRZ 528), was applied to cattle infected with bovine leucosis virus (BLV). An extended period of time was allowed to pass after infection with BLV, which had been checked up through specific serological and virological examinations. The cattle belonged to different age groups and stages of infection (with and without haematological alterations [preleukosis], with incipient tumour development [swelling of externally visible and palpable lymph nodes]). Controls included BLV-infected cows as well as test animals to which isotonic saline had been applied or healthy BLV-free cattle in which the clostridium strain had been used. The serological investigation was carried out in a blind test. 3 of 6 BLV-infected spore-treated heads of cattle responded positively to the cancer test, while the other 3 were negative. The 3 cows with positive cancer test were haematologically and serologically leucosis-positive animals with clinically detectable enlargement of lymph nodes. The 3 negative ones of this group, also serologically and haematologically leucosis-positive, were younger animals without signs of tumorous process. 3 spore-treated BLV-free cows and 2 BLV-infected animals, treated with isotonic saline, were cancer test-negative, as well. Finally, 4 BLV-infected and 2 BLV-free cattle, all of them without spore injection, were completely cancer test-negative. 1 cow of the BLV-infected group did not produce spore antibodies after spore treatment, while 1 cow of the BLV-free untreated control group developed spore antibodies.

Animals↗

[Experiences with DHPG (ganciclovir)--treatment of cytomegalovirus retinitis in AIDS].

Nine patients with unilateral cytomegalovirus (CMV) retinitis were treated with intravenous infusions of the new virustatic drug DHPG (Ganciclovir). The induction dose was 10 mg/kg body weight per day (2-5 weeks). In six cases, a maintenance dose was given thereafter of 5 mg/kg body weight per day. After the induction dose, five patients had visual improvement and satisfactory cicatrization. In one patient, PVR (proliferative vitreous reaction) developed with total tractional retinal detachment. More ocular complications were seen while on longterm therapy: relapses during discontinuation because of leukopenia (three times in two patients), breakthrough (= relapse during maintenance therapy) (one case), serous retinal detachment (one case), and optic atrophy (two cases). The complications caused blindness in two further patients. Only one patient has tolerated maintenance therapy for 22 weeks without having any complications. One patient wanted to have therapy suspended and has remained free of relapse for 28 weeks while on cytostatic therapy. The eyes of two deceased patients were examined histopathologically, immunhistochemically, and ultrastructurally and the findings compared with those of an untreated case. Given at an early stage and without discontinuation, DHPG is an effective means of preventing or delaying blindness caused by cytomegalovirus retinitis in AIDS patients. The directives for an optimal dosage are subject to further prospective randomized clinical studies.

Acquired Immunodeficiency Syndrome↗

[Incidence and pathogenesis of ocular symptoms in HIV infection].

202 patients with HIV infections of different stages [1 (n = 59): symptomless HIV seropositivity, 2 (n = 64): pre-AIDS (LAS = Lymphadenopathy syndrome, ARC = AIDS related complex), 3 (n = 79): AIDS] were prospectively examined. The findings of the first examination were analyzed statistically in a cross-section-study. In 15 AIDS autopsy cases the eyes were examined histopathologically and with immunohistochemical techniques. Patients with stage 1 had only some Sicca syndromes (3%) and neuroophthalmological signs (dyscoria with neurosyphilis) (2%). 14% of the patients with stage 2 had a microvascular retinal syndrome, 11% a Sicca syndrome and 2% neuroophthalmological signs. Among the AIDS patients (stage 3), however, 61% had a microvascular syndrome of the retina, 24% a retinitis resp. choroiditis as an opportunistic infection (in 15% Cytomegalovirus was the causative organism), 16% had neuroophthalmological symptoms, 14% a Sicca syndrome and 5% Kaposi's sarcoma of the eyelids or conjunctiva. The microvascular retinal syndrome was found to be the most sensitive ocular indicator for an advanced stage of HIV infection. Further changes of the anterior eye segments (especially conjunctival vessel abnormalities and precipitates of the corneal endothelium in Cytomegalovirus retinitis) are demonstrated.

Adult↗

Antibacterial immunity and its modeling in experimental tumor tetanus and wound tetanus of the mouse.

The experimental and theoretical analysis of the tumor-tetanus phenomenon has provided us with new insights into the pathogenesis of tetanus infection. Our theoretical model of clostridial propagation in the proliferating tissue is based upon the principle of mitosis-controlled rod division (hit and cloning model). It has lent itself to the description of early growth stages of the clostridial rod population in our experiments of tumor tetanus and of wound tetanus of the mouse. However, the later course of the tetanus lethality curves under antitoxin protection, about a week following injection of the tumor cell-spore or CaCl2-spore suspensions, reveals a pronounced delay in clostridial propagation. Based on our model we can explain this process by a humoral immune reaction directed against the clostridial rods taking into account the variability of elimination of the heterologous tetanus antitoxin applied. The experimental results are in good agreement with those obtained by computer simulation. The theoretical knowledge resulting from these studies can be used for the interpretation of the serodiagnostic tumor test with apathogenic clostridia as well as for the quantitative assessment of the malignancy of neoplastic growth.

Animals↗

Methodological aspects of a serodiagnostic Clostridium tumour test--experience with spontaneous canine tumours.

The paper describes the development of appropriate antigen and method combinations for the microbiological cancer test using the non-oncolysing strain Clostridium butyricum CNRZ 528 in dogs with spontaneous tumours. The diagnostic rod antibodies could be determined quantitatively by the complement fixation test if a short-time warm fixation and a long-time cold fixation procedure were combined in separate runs and if two different antigens, a rod corpuscular antigen and a rod surface antigen, were used. Since complement-fixing antibodies were not always detected in cases of malignant tumours, we additionally used the passive haemagglutination method after pre-absorbing the sera with cross-reacting clostridial antigens. The efficiency of the microbiological cancer test could not be substantially increased, however, by the method combination the reliability of the evaluation of low seropositive titres was improved.

Animals↗