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Biomedical subjects

P Kern

Publications and source records attributed to P Kern.

At least 127 records · Page 7Linked to original sources

Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center.

Prophylactic treatment with fluoroquinolones of patients with profound neutropenia has been found to be useful for preventing gram-negative bacteremia and has become a standard preventive-therapy strategy in many cancer centers, but the development of bacterial resistance is a cause of concern. During the past few years, we have observed an increasing number of patients with leukemia from whom fluoroquinolone-resistant strains of Escherichia coli were isolated. The increase was significant in this patient population, and among patients with other underlying diseases, the rates of isolation of such strains per number of discharges were significantly lower and did not increase. Most of the leukemia case patients (16 of 19) had been pretreated with an oral quinolone (ofloxacin), with cumulative doses until the first isolation of a resistant E. coli strain ranging from 0 to 97.8 g (median, 14.4 g). Repeated isolation of such strains was seen in 8 of 17 patients during a follow-up period of > or = 4 weeks and in 1 of 6 patients during a follow-up period of > or = 16 weeks. Ten patients developed bacteremia (mortality, 1 of 10). On the basis of the number of patients with leukemia admitted to the hematology-oncology service, the incidence of bacteremia caused by fluoroquinolone-resistant E. coli increased from < 0.5% in 1988-1989 and 0.8% in 1990-1991 to 4.5% in 1992-1993 (P < 0.01). MICs for nine isolates obtained from cultures of blood from different patients ranged between 8 and 16 microgram/ml (ciprofloxacin and PD 131628), 8 and 32 microgram/ml (ofloxacin and BAY Y 3118), and 16 and 32 microgram/ml (sparfloxacin) and indicated resistance to trimethoprim-sulfamethoxazole, ampicillin, doxycycline, and chloramphenicol. Of nine isolates obtained from cultures of blood from different patients and that were subjected to genomic DNA typing by pulsed-field gel electrophoresis of XbaI digests, seven were typeable. Among these, four different genotypes were identified, suggesting both the independent development and the horizontal spread of resistant clones of E. coli.

Anti-Infective Agents↗

Leukocyte differentiation antigens in the bone marrow of patients with HIV-related disease.

To understand at what level hematopoiesis is impaired in AIDS patients, we quantitated bone marrow cells of the myeloid and lymphoid lineages in their different stages of differentiation. The bone marrow aspirates of 20 HIV-infected patients (18 with CDC IV) and 11 controls were analyzed by flow cytometry, using a panel of monoclonal antibodies. The mean percentages of CD34+ and CD10+ hematopoietic precursor cells were not significantly altered in the HIV-infected patients. The values of these patients however scattered in a much wider range than in the control group, some patients showing extremely high values. Patients with high levels of CD34+ and CD10+ precursor cells in the bone marrow had lower blood leukocyte counts and lower blood and bone marrow CD4 cell numbers than patients with a low percentage of CD10+ and CD34+ cells (p < 0.01). The percentages of the CD34+ cell subsets studied (CD34+CD33+, CD34+CD14+, CD34+CD15+) were not altered. Bone marrow CD4+ lymphocytes, especially those of CD45RA-phenotype, were reduced, while the CD8+ cells (especially HLA-DR+/CD45RA+ cells) were increased. These results show that the hematologic disorders in AIDS are not simply caused by an altered number or composition of bone marrow precursor cells. We postulate that hematopoiesis is inhibited due to an imbalance in the bone marrow T lymphocyte populations.

Acquired Immunodeficiency Syndrome↗

Inappropriate secretion of antidiuretic hormone and hyponatremia in severe falciparum malaria.

Overhydration can contribute to fatal complications of falciparum malaria, even though renal function may be normal. In this context, the role of inappropriate secretion of antidiuretic hormone (ADH) has been controversial. Therefore, we have analyzed ADH serum concentrations together with serum osmolality and sodium levels in serum and urine of 17 consecutively studied patients with severe falciparum malaria. Serum sodium levels were low in 13 of 17 patients upon admission and returned to normal levels during antiparasitic therapy. Urine sodium levels were low in seven of 13 patients before treatment and increased during therapy. Urine sodium concentrations were high, however, in the remaining six patients. Serum osmolality was lower in these six patients than in the other seven hyponatremic patients (P < 0.002). In relation to serum osmolality, ADH levels were inappropriately high in these six patients, which confirms the presence of inappropriate secretion of ADH. Serum creatinine levels were not higher in these six patients than in those without inappropriate secretion of ADH. Inappropriate secretion of ADH seemed to be a major cause of hyponatremia, since other factors that could lead to this condition were not found in these six patients. In conclusion, we have shown, that human falciparum malaria can be associated with inappropriate secretion of ADH.

Adult↗

Vascular origin of Kaposi's sarcoma. Expression of leukocyte adhesion molecule-1, thrombomodulin, and tissue factor.

We studied seven cases of Kaposi's sarcomas (KS) obtained from patients with AIDS and one KS from a patient without HIV infection. Antigen expression was studied by immunocytochemistry and mRNA expression by in situ hybridisation. The markers tested were endothelial leukocyte adhesion molecule-1, thrombomodulin, and tissue factor. In all tumors (AIDS and non-AIDS associated) these markers reacted positive, indicating transcription and translation of these genes in KS. The synthesis and expression of tissue factor and thrombomodulin suggests that KS is a tumor that has tissue factor-mediated thrombin formation under the control of thrombomodulin. The expression of thrombomodulin and endothelial leukocyte adhesion molecule-1 provides evidence for the vascular origin of KS.

Acquired Immunodeficiency Syndrome↗

[Yersinia enterocolitica infection with extraintestinal manifestations: case report and overview].

Five weeks after a four-day visit to Malta, a 39-year old white male German national developed septic temperatures of up to 40 degrees C, progressive jaundice and a pronounced hepatosplenomegaly. The initial examination showed a very sick, somnolent patient with jaundice, cyanosis, tachypnea and a markedly enlarged liver on both physical examination and sonography. The laboratory evaluation revealed a moderate leukocytosis, markedly accelerated ESR, poor liver function with strongly elevated gamma-GT and alkaline phosphatase levels. Primary antibiotic therapy consisted of doxycycline. Ultrasound examination of the liver four days after admission revealed multiple hypodense abscesses. On the sixth day after admission, gram-negative rods were first isolated from blood cultures; antibiotic therapy was switched to ofloxacin (2 x 400 mg/day) and amoxycillin (3 x 2 g/day) after sensitivity testing. As a result of treatment with this combination of antibiotics, the patient was free of fever 10 days after hospitalization; on the same day yersinia enterocolitica was isolated from the first blood cultures taken on admission. The diagnosis of non-enteric forms of yersinia infection can prove very difficult, especially if the serology is not clear cut and there are no immunological complications. A presentation including intermittent fever, moderate leukocytosis, strongly accelerated ESR and multiple hypodense abscesses in the liver should lead one to consider a non-enteric type of yersinia infection. Hepatic abscesses usually occur in patients who have an iron overload.

Adult↗

Optimizing follicular dendritic cell isolation by discontinuous gradient centrifugation and use of the magnetic cell sorter (MACS).

Follicular dendritic cells (FDC) contribute minimally to the total cell population of lymphatic tissue. In order to obtain higher numbers of viable FDC with only a small fraction of contaminating cells the following procedure was developed. Subsequent to the usual mechanical and enzymatical digestion of human tonsils, single cells were layered on top of a discontinuous bovine albumin gradient and centrifuged at 8500 x g. The suspension collected from the 1.052-1.030 interphase contained an average of 10.5% FDC. Next, the preparation was subjected to a new step involving separation of FDC previously treated with biotin-labelled KiM4 monoclonal antibody, raised against FDC, and attached via biotin-streptavidin bonding to streptavidin-conjugated paramagnetic beads. Purification on a magnetic cell sorter (MACS) yielded 3.3-10.1 x 10(6) cells with an average FDC content of 78.4%. The viability and morphology of the resulting FDC population was examined using trypan blue staining or electron microscopy. This technique will permit in vitro studies and long term cultures with FDC isolated from human lymphatic tissue.

Antibodies, Monoclonal↗

Circulating tumor necrosis factor alpha (TNF), soluble TNF receptors, and interleukin-6 in human subacute bacterial endocarditis.

Cell surface components of viridans streptococci and enterococci have been shown to stimulate the release of tumor necrosis factor alpha (TNF) and interleukin-6 from monocytes/macrophages. In the sera from 10 patients with subacute enterococcal or streptococcal endocarditis, however, the levels of both cytokines were low or undetectable, with elevated TNF levels on admission in 3 patients with complicated disease. Soluble TNF receptor levels were significantly elevated compared with those of healthy controls. When patients with malaria were used as a control group of acute intravascular infection with high circulating TNF values, the ratio between soluble TNF receptors and TNF on admission was significantly greater in the patients with subacute bacterial endocarditis. Besides different amounts of circulating TNF, enhanced TNF receptor shedding may have an important role in the pathogenesis of subacute versus acute clinical disease following human intravascular infection.

Adult↗

Serological differentiation between cystic and alveolar echinococcosis by use of recombinant larval antigens.

Two recombinant antigens of the larval stages of Echinococcus granulosus and Echinococcus multilocularis, termed EG55 and EM10, respectively, were applied for serodiagnosis and serological differentiation between parasitic infections caused by the metacestode tissue of both tapeworms. Antigen EM10 is synthesized by E. multilocularis larvae. Antigen EG55 represents the recombinant form of the low-molecular-weight subunit of antigen B, which is an Echinococcus genus-specific antigen. Both recombinant antigens were expressed as glutathione S-transferase fusion proteins. A sandwich enzyme-linked immunosorbent assay with monoclonal antibodies against EM10 and EG55 as capture reagents for the recombinant antigens was established and was evaluated with 74 serum samples from patients with histologically confirmed alveolar echinococcosis and 63 serum samples from patients with histologically confirmed cystic echinococcosis. A sensitivity of 93.2% and a specificity of 96.8% were achieved for the serodiagnosis of alveolar echinococcosis. Cystic echinococcosis could be detected with a sensitivity of 89.1% and a specificity of 98.6%.

Animals↗

[Lemierre's syndrome with splenic abscesses].

A week after onset of a pharyngo-tonsillitis a previously healthy 23-year-old man developed high fever (41.4 degrees C), leukocytosis (12,200/microliters) with marked shift to the left, thrombocytopenia (86,000/microliters) and increased transaminases (GOT 83 U/l, GPT 113 U/l). Chest x-ray film suggested intrapulmonary abscesses with left-sided pleural effusion. The suspected diagnosis of "post-tonsillitis" septicaemia (Lemierre's syndrome) was confirmed by demonstrating anaerobic, fusiform, gram-negative bacteria (Fusobacterium nucleatum and necrophorum) in several blood cultures. Despite antibacterial treatment (amoxicillin/clavulanic acid, imipenem/cilastatin, clindamycin) he had recurrent pain referred to the kidney region and persisting fever. Repeated ultrasound and radiological examinations revealed new foci in the spleen, which were enlarging. Laparotomy with splenectomy performed on day 17 after the begin of treatment confirmed multiple splenic abscesses, but abscess pus and splenic tissue were sterile. After altogether 6 weeks of antibiotic treatment, finally with chloramphenicol, the patient was discharged in a good general state.

Abscess↗

[Clinical diagnosis and neuropathologic examination findings in 20 AIDS patients].

Disorders of the central nervous system (CNS) associated with HIV infections are becoming increasingly important in the area of clinical diagnosis and treatment of patients with AIDS. The aim of this retrospective analysis of 20 patients with AIDS who died in 1989 was to compare clinical diagnosis, neuroradiological findings and treatment with the results of neuropathological studies. The neuropathological examinations revealed primary CNS lymphoma (high-grade non-Hodgkin's lymphoma) in seven cases, cerebral toxoplasmosis in four cases, haemorrhagic infarction in three cases, cerebral cryptococcosis in three cases, and one case each of infiltration of the dura by a peripheral Burkitt's lymphoma, cytomegalovirus encephalitis and bacterial meningitis. A remarkably high percentage of CNS lymphomas with no distinct clinical or neuroradiological differentiation criteria were found in this study. On the basis of these data, we conclude that stereotactic biopsy and histological diagnosis should be recommended for patients with focal intracerebral lesions who fail to respond to suitable anti-parasitic treatment.

AIDS Dementia Complex↗

UVA- and UVB-induced changes in collagen and fibronectin biosynthesis in the skin of hairless mice.

The modifications induced in hairless mouse skin by chronic UV irradiation were investigated. Skin explant cultures were used to study UVA- and UVB-induced changes occurring in interstitial collagen (type I and type III) and fibronectin biosynthesis. To study the long-term effects, albino hairless mice were irradiated with UVA radiation alone from two sources with different spectral qualities or with UVB. UVA and UVB radiation produced a significant increase in the ratio of type III to type I collagen (more than 100% for UVA-irradiated skin and about 60% for UVB-irradiated skin) accompanied by a significantly increased fibronectin biosynthesis (50% or more in all irradiated groups). Irradiation with either UVA or UVB alone had no significant effect on the total collagen synthesis and resulted in only a slight decrease in the total collagen content of the skin determined as hydroxyproline. This decrease was significant only in the case of the group irradiated with UVA (xenon) (decrease of 25%, expressed as micrograms of hydroxyproline per milligram wet weight). A significant decrease in collagen hydroxylation (expressed as radioactive hydroxyproline/radioactive hydroxyproline plus proline in neosynthesized collagen) was observed of about 50% in skin irradiated with UVA (xenon) but not in UVB-treated skin. Several of the above modifications (increased fibronectin biosynthesis, increased collagen type III to type I ratio) correspond to the modifications observed during the aging of non-irradiated hairless mice. Therefore it appears that UV irradiation accelerates the modifications of extracellular matrix biosynthesis observed during aging.

Amino Acids↗

[Long-term therapy of cystic liver echinococcosis with mebendazole].

Surgery is the therapy of choice in the treatment of infestations with Echinococcus (E.) granulosus and E. multilocularis. Chemotherapy with mebendazole, a benzimidazole derivative, introduced 1976 in the therapy of human echinococcosis, showed good results only in cases of infestation with E. multilocularis. In the cases of liver cysts, caused by E. granulosus, the treatment with mebendazole did not succeed as well. Between 1977 and 1986, 44 patients, suffering from infestations with E. granulosus, were referred to the Clinical Department of the Bernhard-Nocht-Institut. In a retrospective study, the data of seven patients had been evaluated: They had not undergone surgery because of the size of the lesions or because they refused the operative treatment. Receiving mebendazole as the only therapy, they had been treated and followed up for more than four years. Mebendazole was given in a dosage of 50 mg/kg body weight in repeated cycles of one month's duration followed by a treatment-free interval of two months. After a median of 55 months (median 13 effective treatment months) six of the seven patients presented a therapeutical success as demonstrated by ultrasound and computed tomography. The cystic lesions had dissolved or decreased in size considerably. One case showed unaltered findings of the liver lesion. Mebendazole treatment was well tolerated by all patients. If the size of the cystic liver-lesions excludes a curative operative treatment or if the patient refuses surgery, the indication for chemotherapy with mebendazole is given.

Adult↗

[Malaria tropica].

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Exchange Transfusion, Whole Blood↗

Prevalence of antibodies to recombinant virion infectivity factor in the sera of prospectively studied patients with HIV-1 infection.

Two hundred twenty-four sera were collected from 34 HIV-1 infected patients during an observation period of up to 4.5 years (109 patient years of observation). The sera were tested for the presence of antibodies against the HIV-1 virion infectivity factor (vif) protein. Thirty sera from 6 HIV-1 seronegative individuals served as negative controls. The sera were immunoblotted against a recombinant, prokaryotically expressed vif protein. The prevalence of anti-vif antibodies increased significantly with progression of the disease from 18% to 81% (P less than 0.0001) which suggests a possible role of vif in HIV-1 replication and pathogenicity.

Biomarkers↗