Biomedical subjects
J O Gebbers
Publications and source records attributed to J O Gebbers.
[Barrett's esophagus: diagnosis and therapy].
Barrett's esophagus is usually diagnosed by the endoscopic and histological finding of columnar epithelium with intestinal metaplasia in the distal esophagus. The prevalence of Barrett's esophagus (long segment) is <2% in the general population and 3-5% in patients with chronic reflux symptoms. Barrett mucosa predisposes patients to adenocarcinoma that develops in approximately 0.5% of these patients per year (Barrett mucosa --> dysplasia --> cancer sequence). The incidence of esophageal adenocarcinoma over the past few decades; the present incidence, however, is still rather low and is reported to be approximately 4 and approximately 0.5 per 100,000 in males and females, respectively. The malignant potential of the Barrett mucosa increases with dysplastic changes. Guidelines for surveillance and therapy are based on the presence and the degree of dysplastic lesions. Long-term studies on cost-effectiveness of these guidelines are, however, still missing.
[Langerhans cell histiocytoses: 50 years to histiocytosis X].
Histiocytoses encompass a heterogeneous group of histiocytic disorders that may be separated in a group of variable biological behaviour and in a clearly malignant group. The histopathologic diagnosis of all types of histiocytoses is always mandatory. The 50-year-old Histiocytosis X compiles a subgroup of different biological behaviour, nowadays called Langerhans cell histiocytoses--the subject of the review. It has a wide range of manifestations: self-healing cutaneous, benign solitary and malignant systemic manifestations require the staging in order to evaluate a possibly necessary therapy. Chemotherapy should be performed within international protocols.
[Abortion in humans caused by Chlamydophila abortus (Chlamydia psittaci serovar 1)].
On a farm housing cattle and goats an abortion storm occurred affecting 50% of the goats during the lambing season 2000/2001. In one of three investigated caprine abortions Chlamydophila abortus could be identified as etiology. During this time a pregnant woman (pregnancy week 19/20) had contact with aborting goats. She developed a severe generalized infection and aborted. The placenta contained Chlamydophila abortus shown by immunohistochemistry and PCR. Aim of the present case report is to alert veterinarians about the potential zoonotic risk of ovine/caprine abortions.
[Cor bovinum: decreased incidence over the last 20 years--a therapeutic success?].
BACKGROUND: The Cor bovinum (CB), a heart of > 500 g, is often found in patients with clinically unclear cause of death. Cardiomyocyte hypertrophy and increase of the interstitial connective tissue can lead to electromechanical instability and consecutive sudden heart death. METHODS: This retrospective, autopsy-protocol-based study compared the frequency of altogether 415 CB and associated pathologies in two 4-year periods (1978-1981 and 1997-2000), including only patients of the Clinic of Internal Medicine (n = 1181 autopsies). RESULTS: A CB was found in 25.3% of the patients of the first period (1978-1981) in contrast of 20.6% in the second period (1997-2000); hence, the frequency of CB is decreasing (0.05 > p > 0.02). The mean age at death was 67.7 years in 1978-1981 and 74.3 years in 1997-2000; this revealed an increasing trend (p < 0.001). The male-female proportion was 4:1. In 93% of all patients with CB, we found coronary atherosclerosis as a sign of high blood pressure and in 79% a COPD. In 84% of all cases with CB the cause of death was directly related to the CB, in 37% of these patients the cause of death was clinically unclear. CONCLUSIONS: The CB is a decreasing but still frequent autopsy-finding. We consider high blood pressure, COPD and male sex as the main risk factors. The decrease in frequency of CB and the increase in age at death might be interpreted as the effect of a successful application of new therapeutic standards in the last two decades (ACE-inhibitors, beta blockers, statins, PTCA, surgical heart interventions).
[The environment and autoimmunity--from external causes to inner conflicts].
Autoimmune disorders result from a breakdown of immunologic tolerance leading to an immune response against self-molecules. In most instances the events that initiate the immune response to self-molecules are unknown, but a number of studies suggest associations with environmental and genetic factors and certain types of infections. The concordance of autoimmune diseases among identical twins is virtually always less than 50%, often in the 25-40% range. This observation, as well as epidemic clustering of some autoimmune diseases following xenobiotic exposure, reinforces the thesis that autoimmune disease is secondary to both genetic and environmental factors. In addition, because of individual genetic susceptibilities based not only on major histocompatibility complex differences but also on differences in toxin metabolism, lifestyles, and exposure rates, individuals will react differently to the same chemicals. With these comments in mind it is important to note that there have been associations of a number of xenobiotics with human autoimmune disease, including mercury, iodine, vinyl chloride, canavanine, organic solvents, silica, L-tryptophan, particulates, ultraviolet radiation, and ozone. In addition, there is discussion in the literature that raises the possibility that xenobiotics may also exacerbate an existing autoimmune disorder. In this article these issues are discussed, in particular, the evidence for the role of environmental agents in the initiation or progression of autoimmune conditions. With the worldwide deterioration of the environment, this is a particular important subject for human health. This is best illustrated by the epidemics of eosinophilic myalgia syndrome with shared characteristics that occurred about 20 years ago. Another example is the toxic oil syndrome of Spain in 1981 involving cooking oil led to both acute and chronic disease as well as formation of auto-antibodies to collagen, DNA, and skeletal muscle. Currently the question is risen whether there is a link between environmental estrogens and autoimmune disorders, especially since these illnesses are reported possibly more frequent. Yet for the time being, an answer is not available, since the current state of science with respect to autoimmunity and environmental agents is still in the early stages of hazard identification.
[Castleman disease].
BACKGROUND: The term "Castleman's disease" (angiofollicular lymph node hyperplasia) comprises a heterogeneous clinicopathologic entity among lymphoproliferative disorders. CASE REPORT: We present a rare case with retroperitoneal manifestations, and discuss several aspects of diagnosis, differential diagnosis, the clinical course and therapy of the disease. Finally, we summarize the actual knowledge about the pathogenesis of Castleman's disease.
Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin.
The evaluation of peptide receptors in man is needed not only to discover the physiological target tissues of a given peptide but also to identify diseases with a sufficient receptor overexpression for diagnostic or therapeutic interventions. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptors have been evaluated in human tumors and in their tissues of origin using in vitro receptor autoradiography with 125I-VIP or 125I-acetyl-PACAP-27 in tissue sections. The VIP/PACAP receptor subtypes VPAC1, VPAC2, and PAC1 were evaluated in these tissues by determining the rank order of potencies of VIP and PACAP as well as VPAC1- and VPAC2-selective analogues. The VIP/PACAP receptors expressed in the great majority of the most frequently occurring human tumors, including breast (100% receptor incidence), prostate (100%), pancreas (65%), lung (58%), colon (96%), stomach (54%), liver (49%), and urinary bladder (100%) carcinomas as well as lymphomas (58%) and meningiomas (100%), are predominantly of the VPAC1 type. Their cells or tissues of origin, i.e., hepatocytes, breast lobules and ducts, urothelium, prostate glands, pancreatic ducts, lung acini, gastrointestinal mucosa, and lymphocytes, also predominantly express VPAC1. Leiomyomas predominantly express VPAC2 receptors, whereas paragangliomas, pheochromocytomas, and endometrial carcinomas preferentially express PAC1 receptors. Conversely, VPAC2 receptors are found mainly in smooth muscle (i.e., stomach), in vessels, and in stroma (e.g., of the prostate), whereas PAC1 receptors are present in the adrenal medulla and in some uterine glands. Whereas the very wide distribution of VIP/PACAP receptors in the normal human body is indicative of a key role of these peptides in human physiology, the high VIP/PACAP receptor expression in tumors may represent the molecular basis for clinical applications of VIP/PACAP such as in vivo scintigraphy and radiotherapy of tumors as well as VIP/PACAP analogue treatment for tumor growth inhibition.
The comet assay of nasal epithelia: measurement of DNA damage for the assessment of genotoxic air pollution.
OBJECTIVES: The alkaline single cell gel electrophoresis or "comet" assay allows measurement of DNA damage in single cells with a high degree of sensitivity, e.g., for investigations of the effect of environmental agents with DNA-damaging potential. This study aimed to adapt this test to respiratory cells of the human nasal mucosa to examine the genotoxic effect of air pollution (cigarette smoke). STUDY DESIGN: In a prospective study, nasal epithelia of 16 cigarette smokers were examined by the adapted comet assay and the results were correlated with the results of the Papanicolaou-stained nasal cytology, carried out in a blinded fashion. The control group comprised 20 non-smoking men. All subjects under investigation were healthy office workers. METHODS: Nasal epithelia were harvested from the maxilloturbinates. One part of cells was Papanicolaou stained and evaluated by cytopathologists. The comet assay was performed on the other part of the cells. The examiners were blinded to the study and control groups. RESULTS: Among cigarette smokers, a significant correlation between cytopathological cell nucleus changes (metaplasia and dysplasia) and the DNA migration (tail lengths) in the comet assay was found as a sign of DNA damage. This was not found in nonsmoking control persons. CONCLUSIONS: These results confirm the sensitivity of the comet assay and the hypothesis that cell nucleus changes in conventional nasal cytology are associated with DNA damage.
The nose as bacterial reservoir: important differences between the vestibule and cavity.
UNLABELLED: The difference between the spectra of potential bacterial pathogens (PBPs) in the nasal vestibule and cavity has not been taken into account in clinical studies. PURPOSE: Since one can anticipate different flora in different kinds of mucosae, the authors compared bacterial species in the vestibule with those of the cavity. SUBJECTS AND METHOD: A total of 534 healthy male clerical workers in a downtown Lucerne office building were examined with fractionated swabs. RESULTS: PBPs, notably Staphylococcus aureus, were found in 412 subjects and surprisingly, differences in flora of the two sites were noted in 130 of them: PBPs were observed in the vestibule and not in the cavity in 85 of the subjects, and in 45 of them, the reverse was true. CONCLUSION: The practical implications of these findings are considerable regarding infection control in patients at increased infection risk.
Fatal varicella-zoster virus antigen-positive giant cell arteritis of the central nervous system.
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[Gastric carcinoid--pathogenesis and treatment].
Gastric carcinoid tumours are rare neoplasms of neuroendocrine origin. They are believed to grow from enterochrommaffin-like (ECL) cells. Three different types of tumours can be distinguished: type I: hypergastrinaemic, induced by achlorhydria in chronic atrophic gastritis; type II: hypergastrinaemic, associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia syndrome type 1; type III: sporadic. The trophic effect of gastrin on ECL cells is of crucial importance in the pathogenesis and treatment of hypergastrinaemic carcinoids. In these patients, hypergastrinaemia leads to ECL-hyperplasia, -dysplasia and -neoplasia. Hypergastrinaemic carcinoids often follow a very benign course, which makes it possible to avoid surgery, at least in patients at high surgical risk. The management of these three types is discussed.
[Multiple gastric carcinoid tumors in chronic atrophic gastritis: long-term follow-up under conservative management].
A 68-year-old patient presenting with non-specific abdominal symptoms was diagnosed as having multiple gastric carcinoid tumours with H. pylori-positive chronic atrophic gastritis and hypergastrinaemia. No metastases were found. As he was inoperable due to comorbidity, conservative management was instituted. The patient was followed for 6 years without signs of tumour progression. He eventually died from an unrelated cause. This case shows that hypergastrinaemic carcinoids may follow a benign course and do not necessitate aggressive surgical management, at least in poor risk patients.
Monoclonal plasma and Mott cells in a rectal adenoma.
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Phase 1 evaluation of intranasal virosomal influenza vaccine with and without Escherichia coli heat-labile toxin in adult volunteers.
Virosomal vaccines were prepared by extracting hemagglutinin (HA) and neuraminidase from influenza virus and incorporating it in the membranes of liposomes composed of phosphatidylcholine. Two intranasal spray vaccine series were prepared: one series comprised 7.5 micrograms of HA of each of three strains recommended by the World Health Organization and 1 microgram of Escherichia coli heat-labile toxin (HLT), and the other contained the HA without HLT. In addition, a third vaccine preparation contained 15 micrograms of HA and 2 micrograms of HLT. The parenteral virosomal vaccine contained 15 micrograms of HA without additional adjuvant. The immunogenicity of a single spray vaccination (15 micrograms of HA and 2 micrograms of HLT) was compared with that of two vaccinations (7.5 micrograms of HA with or without 1 microgram of HLT) with an interval of 1 week in 60 healthy working adults. Twenty volunteers received one parenteral virosomal vaccine. Two nasal spray vaccinations with HLT-adjuvanted virosomal influenza vaccine induced a humoral immune response which was comparable to that with a single parenteral vaccination. A significantly higher induction of influenza virus-specific immunoglobulin A was noted in the saliva after two nasal applications. The immune response after a single spray vaccination was significantly lower. It could be shown that the use of HLT as a mucosal adjuvant is necessary to obtain a humoral immune response comparable to that with parenteral vaccination. All vaccines were well tolerated.
Neuropathology of ablation of rat gliosarcomas and contiguous brain tissues using a microplanar beam of synchrotron-wiggler-generated X rays.
Adult-rat-brain tissues display an unusually high resistance to necrosis when serially irradiated with parallel, thin slices of a microplanar (i.e., microscopically thin and macroscopically broad) beam of synchrotron-wiggler-generated, approx. 35-120 keV (median approx. 50 keV) Gd-filtered X rays at skin-entrance absorbed doses of 312 to 5000 Gy per slice. Such microplanar beams were used to irradiate young adult rats bearing right frontocerebral 9L gliosarcomas (approx. 4 mm diameter), through a volume of tissue containing the tumor and contiguous brain tissue, either in a single array or in 2 orthogonally crossed arrays of tissue slices. Each array included 101 parallel microplanar slices, 100 microm center-to-center distance, each slice being approx. 25 microm wide and 12 mm high, with skin-entrance absorbed doses of 312.5 Gy or 625 Gy per slice. Compared with unirradiated controls with a median survival time of 20 days after tumor initiation, the median survival time was extended in irradiated rats by 139 days (625 Gy, crossed arrays), 96 days (312 Gy, crossed arrays) or 24 days (625 Gy, single array). The tumors disappeared in 22 of the 36 irradiated rats, 4/11 even after unidirectional microbeam irradiation. The extent and severity of radiation damage to the normal brain in rats with or without tumor was graded histopathologically. Correlation of those grades with radiation doses shows that loss of tissue structure was confined to beam-crossing regions and that only minor damage was done to zones of the brain irradiated unidirectionally.