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K Dalhoff

Publications and source records attributed to K Dalhoff.

At least 73 records · Page 4Linked to original sources
PubMed1998

Early T-cell apoptosis and Fas expression during antiretroviral therapy in individuals infected with human immunodeficiency virus-1.

Several lines of evidence suggest that Fas-mediated apoptosis is involved in the CD4 T-cell depletion in human immunodeficiency virus-1 (HIV-1) infection. To investigate this, we studied changes in peripheral blood, early T-cell apoptosis and Fas expression after initiation of antiretroviral therapy (ART) in 18 HIV-1-infected individuals. Flow cytometric analysis was performed with Apostain and CD4, CD8 and Fas staining. Fas expression was quantified by standardized beads. The levels of CD4 and CD8 T cells with early apoptosis were increased comparably in HIV-1-infected individuals. Despite elevated CD4 T cell counts, no decline in early T-cell apoptosis could be detected during the first 8 weeks of ART. However, after 26 weeks of ART in five patients that showed a sustained reduction of viral replication there was a marked decrease in T cells with features of early apoptosis. No difference was found for Fas expression on early apoptotic T cells. Fas expression on CD4 and CD8 T cells was reduced after initiation of ART; this was independent of the CD4 T-cell trend and indicates that the immediate CD4 T-cell expansion during ART is probably not the result of a decreased rate of early apoptosis among peripheral blood CD4 T cells. However, preliminary data imply a long-term reduction of early T-cell apoptosis and Fas expression in patients who show a sustained reduction of viral replication.

Adult↗
PubMed1998

Inhibition of neutrophil apoptosis and modulation of the inflammatory response by granulocyte colony-stimulating factor in healthy and ethanol-treated human volunteers.

Granulocyte colony-stimulating factor (G-CSF) has immunomodulating properties that could be beneficial for adjunctive treatment of severe infections. Cytokine release from stimulated whole blood and expression of neutrophil surface and apoptosis markers in response to G-CSF were studied in human volunteers under physiologic conditions and after ethanol pretreatment. Levels of interleukin (IL)-1 receptor antagonist and soluble tumor necrosis factor (TNF) receptor-1 were significantly increased after G-CSF, whereas TNF-alpha and IL-10 concentrations were reduced, and IL-1beta and IL-8 remained unchanged. There was a significant inhibition of neutrophil apoptosis and increased expression of complement regulatory protein CD55 without changes in CD11b, CD14, and CD59 expression. These effects were well preserved after ethanol pretreatment, which per se led to an increase in apoptosis and decreased CD55 expression. Thus, G-CSF treatment was associated with a reduction of the proinflammatory cytokine response and enhanced neutrophil survival in vivo, suggesting a therapeutic potential of G-CSF for severe infections in the nonneutropenic host.

Adult↗
PubMed1998

Interaction of Chlamydia pneumoniae and human alveolar macrophages: infection and inflammatory response.

The obligate intracellular pathogen Chlamydia pneumoniae is associated with chronic respiratory, atherosclerotic, and rheumatic disease. The alveolar macrophage (AM) is a potential target cell for the pathogen and may contribute to respiratory immunopathology. We therefore investigated in vitro the interaction between chlamydiae and macrophages with cocultures of C. pneumoniae and AM from 12 healthy volunteers. Inflammatory responses were evaluated through lucigenin-amplified chemiluminescence; secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin 8 (IL-8); and expression of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen-DR (HLA-DR). C. pneumoniae readily induced productive infection in the AM. Inclusions containing replicating pathogens could be maintained for up to 120 h. Morphologically similar infection patterns were seen ex vivo in AM collected from six patients with known C. pneumoniae pneumonia. AM responded to the infection with a marked, dose-dependent release of reactive oxygen species, TNF-alpha, IL-1beta, and IL-8. ICAM-1 expression remained unchanged, but HLA-DR was significantly upregulated. Our data indicate that the release of antimicrobial mediators cannot prevent chlamydial infection and replication in AM, but may be involved in amplification of the local inflammatory response in C. pneumoniae pneumonia.

Adult↗
PubMed1998

[Incidence of bacterial pneumonia in HIV-positive patients treated with preventive co-trimoxazole or pentamidine].

BACKGROUND: Besides Pneumocystis carinii bacterial pathogens represent the most common aetiology of pulmonary infections in HIV-positive patients. However, the impact of PCP prophylaxis on the incidence of bacterial pneumonia in HIV-positive patients using pentamidine or co-trimoxazole is still unknown. PATIENTS AND METHODS: We analysed retrospectively the data of 80 consecutive HIV-positive patients with a CD4-cell count < 300/microliter. The total observation period was 1993 patient months. Type and duration of chemoprophylaxis, frequency of bacterial pneumonia, PCP, extrapulmonary bacterial infections and cerebral toxoplasmosis were documented in a standardised manner. For statistical analysis we used the Kaplan-Meier test for the time to a recurrence of the various infections under both prophylaxis regimens and the Odds ratio for determination of the relative risk. RESULTS: We followed up 47 patients inhaling 300 mg pentamidine monthly for a total of 1133 months and 33 patients taking 480 mg co-trimoxazole per day p.o. for a total of 860 months. There were no statistically significant differences between the two groups in respect of demographic parameters, stage and therapy of HIV infection and distribution of risk groups. We found seven bacterial pneumonias in the co-trimoxazole group and 13 in the pentamidine group (not significant); the most common causative organisms were S. pneumoniae (n = 4), S. aureus (n = 3) and H. influenzae (n = 3). Furthermore, in the pentamidine group 12 PCP and nine cases of toxoplasma encephalitis were observed, whereas none of these infections occurred in the co-trimoxazole group (p < 0.05). Two of the patients taking co-trimoxazole and 15 of those inhaling pentamidine had extrapulmonary bacterial infections (p < 0.05), the most frequently identified pathogen being S. aureus (n = 7). The two prophylaxis groups did not differ significantly with regard to laboratory data, course and therapy of the bacterial pneumonias. CONCLUSION: There was no significant influence of chemoprophylaxis on the incidence of bacterial pneumonia in patients with advanced HIV-disease in our study. Since S. pneumoniae represents the most common causative agent, we suggest immunisation with a polyvalent pneumococcal vaccine at an early stage of HIV-infection.

AIDS-Related Opportunistic Infections↗
PubMed1997

Production of reactive oxygen species by central venous and arterial neutrophils in severe pneumonia and cardiac lung edema.

OBJECTIVE: In pneumonia the influx of neutrophils to the lungs is thought to be of primary importance with regard to host defence and to complications like the adult respiratory distress syndrome. We wanted to evaluate the neutrophil function in patients in acute respiratory failure who required admission to the intensive care unit. DESIGN: We determined the luminolenhanced chemiluminescence (CL) of neutrophils isolated both from central venous and arterial blood. In addition, the plasma-concentrations of alpha 1-proteinase inhibitor, (alpha 1PI), alpha 2-macroglobulin (alpha 2PI) and elastase-alpha 1PI-complex (elastase) were determined by chemiluminescence immunoassay, and the intracellular elastase content of blood neutrophils was determined using immuno activation assay. PATIENTS: 28 Patients, 18 with acute pneumonia (group 1) and 10 with cardiac pulmonary edema (group 2). MEASUREMENTS AND RESULTS: In group 1, luminol enhanced CL was significantly higher than in group 2 (mean 87.7 vs 30.4 x 10(6) counts per minute, p < 0.01). The production of reactive oxygen species was significantly higher in central venous than in arterial neutrophils in the patients with pneumonia (p < 0.03). In patients with pulmonary edema there was no such difference. The plasma concentration of elastase in group 1 was significantly higher than in group 2, that of alpha 2PI were significantly lower. The intracellular elastase content of neutrophils was lower in group 1 than in group 2. In group 1, there was a trend for a correlation between lower intracellular elastase content and a higher elastase plasma concentration. There were no central venous-arterial differences with regard to leukocyte count, cell differential or protein concentration in either group. CONCLUSION: The central venous-arterial differences in neutrophil production of reactive oxygen species support the concept of compartmentalization of activated neutrophils from the systemic to the pulmonary compartment.

Adult↗
PubMed1997

Plasma cholecystokinin and its precursors in hepatic cirrhosis.

BACKGROUND/AIMS: The liver influences the metabolism of several peptide hormones. The metabolic effect may, however, change considerably by diseases in the liver. This study examined whether hepatic cirrhosis influences the occurrence and concentrations of procholecystokinin (proCCK) and its products in plasma. METHODS: The sum of proCCK and its products (both processing intermediates and bioactive fragments) in plasma were measured by a recently developed "processing-independent analysis". Bioactive forms of CCK in plasma were measured using a highly specific radioimmunoassay directed against the C-terminal epitope of CCK. RESULTS: In plasma from patients with primary biliary cirrhosis the basal concentration of the total proCCK product was increased. Moreover, a mixed meal increased plasma concentrations of both bioactive CCK (i.e. carboxyamidated an 0-sulfated CCK peptides) and the total proCCK product in primary biliary cirrhosis. In contrast, plasma concentrations of bioactive CCK and the total proCCK product were normal in patients with alcoholic liver cirrhosis-both pre- or postprandially. The fraction of bioactive CCK in plasma from patients with both biliary and alcoholic cirrhosis was also normal. Hence, in primary biliary cirrhosis, alcoholic cirrhosis and in controls, respectively, bioactive CCK constituted 15%, 15% and 17% of the total proCCK product in the basal state; 70%, 58% and 53% 30 min after and 48%, 56% and 51% 90 min after the meal. As shown by gel chromatography, plasma from patients with primary biliary cirrhosis and controls sampled 30 min after a meal contained CCK-33, -22 and -8-like peptides. In addition, plasma contained non-amidated (approximately non-bioactive) proCCK products corresponding in size to CCK-83, -58 and -33. Ninety minutes after a meal, CCK-8 predominated in plasma from patients with primary biliary cirrhosis, whereas plasma from controls displayed a CCK profile similar to that obtained 30 min post-prandially. CONCLUSIONS: The results show that CCK-8 is metabolized at a slower rate in patients with primary biliary cirrhosis.

Adult↗
PubMed1997

Expression of liver functions following sub-lethal and non-lethal doses of allyl alcohol and acetaminophen in the rat.

BACKGROUND/AIMS: To relate severity of intoxication with allyl alcohol and acetaminophen to modulated hepatic gene expression of liver functions and regeneration. METHODS: Rats fasted for 12 h received acetaminophen 3.5 or 5.6 g per kg body weight, or allyl alcohol 100 or 125 microl by gastric tube, doses producing no and about 30% mortality, respectively, within 2 days. In the morning 2, 6, 12, 24, and 36 h after intoxication, RNA was extracted from liver tissue. By slot blot hybridization mRNA levels were determined for acute phase proteins, enzymes involved in ammonia elimination and urea synthesis, and for proteins related to liver regeneration. RESULTS: After allyl alcohol, mRNA of "positive" acute phase proteins was higher than after acetaminophen and increased with the dose, whereas after acetaminophen it decreased with the dose. The mRNA of the urea cycle enzymes and glutamine synthetase was uniformly reduced by allyl alcohol, whereas that of most urea cycle enzymes was above the controls after the non-lethal, but not after the sub-lethal, dose of acetaminophen. The mRNA of glutamine synthetase was significantly more reduced by acetaminophen than by allyl alcohol. The mRNA of cell-cycle dependent proteins was greatly reduced after both toxins, more after the higher dose. CONCLUSIONS: The study shows that acetaminophen intoxication inhibits or fails to induce the expression of acute phase proteins in contrast to allyl alcohol intoxication. Allyl alcohol suppressed the expression of urea cycle enzymes, whereas that of the rate limiting enzymes carbamoylphosphate synthase and argininosuccinate synthetase was increased by the non-lethal but not by the sub-lethal dose of acetaminophen. The expression of the cell-cycle dependent proteins was more suppressed after the sub-lethal than after the non-lethal dose of both toxins. The data support the view that a fatal outcome of the intoxications depends more on the ability to regenerate than on the maintenance of liver-specific functions.

1-Propanol↗
PubMed1997

Different BALF protein composition in normal children and adults.

UNLABELLED: Quantification of proteins in bronchoalveolar lavage fluid (BALF) is being performed increasingly, because of their potency in elucidating pathophysiological processes and their possible clinical relevance. STUDY POPULATION: 37 normal children (12 female, 25 male, mean age +/- SD 7.9 +/- 3.5 years, range 3-16 years) undergoing elective surgery for nonpulmonary illnesses and 16 healthy adults (all male, mean age +/- SD 24.7 +/- 2.6 years, range 20-28 years, 8 smokers, 8 nonsmokers) have been studied after approval by the ethics committees of both institutions. METHODS: BAL was performed with normal saline in the right middle lobe or one of its segments. Lavage volume was 15 x 20 ml in adults and 3 x 1 ml/kg in children. In adults the first aliquot was processed separately, 2 aliquots of the following were pooled (resulting in 8 different fractions) so that different lavage protocols could be calculated. The concentrations of the plasma-proteins alpha 1-proteinase inhibitor (alpha-1PI), alpha 2-macroglobulin (alpha 2PI), albumin (Alb) and of the locally released proteins myeloperoxidase (MPO), lactoferrin (Lf), elastase (Ela) and fibronectin (Fib) were determined in BALF using chemiluminescence immunoassays. RESULTS: The BALF concentrations of the plasma proteins were higher in children compared to adults. In contrast, concentrations of the locally released proteins were similar in both groups. Protein concentrations in the first recovered aliquot were different from the following in healthy adults with higher values of MPO, Lf and Ela and lower concentrations of alpha 1PI, alpha 2PI and Alb. Subsequent aliquots did not show a progressive dilution of these proteins with increasing lavage volumes. In smokers, BALF concentrations of albumin, alpha 1PI and MPO were higher compared to nonsmokers. CONCLUSION: BALF protein concentrations are different in normal children and adults. These results underscore the necessity to establish independent reference values for children, as could be demonstrated earlier with regard to BAL cell composition.

Adult↗
PubMed1997

Pentoxifylline in treatment of sarcoidosis.

The optimal therapy for sarcoidosis remains unclear. Most patients show a short-term response to corticosteroid therapy, but they have to face the risk of significant side effects. Because tumor necrosis factor alpha (TNF) plays a critical role in granuloma formation and sustenance as well as in the progression of sarcoidosis, we investigated pentoxifylline (POF), which exerts TNF-inhibitory activity, as a therapeutic agent in active pulmonary sarcoidosis. Twenty-three previously untreated patients with documented disease progression during the preceding 3 mo were treated with POF (25 mg/kg daily) and followed for 6 mo of therapy. Two patients were lost to follow-up, and three patients discontinued POF therapy because of gastrointestinal side effects; 18 patients were thus evaluated. Eleven patients improved, seven remained stable and, most importantly, none deteriorated. Lung function tests-DL(CO), Pa(O2) and Pa(O2)[exercise]-were significantly improved in the patient group as a whole and increased in a highly significant manner in those who improved. Three patients with corticosteroid-resistant disease progression were additionally treated with a combination of corticosteroids with POF. In all three patients the combination therapy resulted in an immediate complete decrease of disease activity, even after tapering prednisone to 7.5 mg daily or tapering off corticosteroids. These promising results suggest that POF may improve therapeutic regimens in pulmonary sarcoidosis either by sparing or replacing corticosteroids.

Adult↗
PubMed1997

Expression of complement receptors and regulatory proteins on alveolar CD4+ lymphocytes from human immunodeficiency virus-1 infected individuals.

Several lines of evidence suggest a dysregulation of the complement system in human immunodeficiency virus-1 (HIV-1) infected patients. The aim of this study was to elucidate whether CD4+ alveolar lymphocytes from HIV-1 infected patients show a loss of complement regulatory proteins that would render these cells susceptible to antibody-dependent complement-mediated cytotoxicity. We investigated the expression of complement regulatory (CD46, CD55, CD59) and complement receptor (CR1, CR2, CR3, CR4) proteins on alveolar cells by flow cytometry. Cells were obtained by bronchoalveolar lavage from 17 HIV-1 infected and 12 HIV-1 negative individuals. Expression of adhesion molecules (leucocyte functional associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1)) and CD30 were evaluated in patient subgroups. In addition, interleukin (IL)-1beta, tumour necrosis factor alpha (TNF-alpha), IL-4 and interferon gamma (IFN-gamma) concentrations were measured in supernatants of alveolar cells. We found a significantly reduced expression of CD46 and CD59 on CD4+ alveolar lymphocytes from HIV-1 infected individuals, whereas the expression of CR3, CR4, ICAM-1 and CD30 was increased. IL-1beta and TNF-alpha concentration in supernatants of alveolar cells was augmented in HIV-1 infected patients, but did not correlate with the expression of surface molecules. IFN-gamma concentration was also increased and showed an inverse relationship to the surface expression of CD30 on CD4+. Our data suggest that in human immunodeficiency virus-1 infection an increased level of activation is associated with a diminished expression of complement regulatory proteins on CD4+ alveolar lymphocytes. This phenomenon might contribute to the depletion of CD4+ lymphocytes and the local immunodeficiency in the pulmonary compartment.

Adult↗
PubMed1997

Efficacy of transbronchial biopsy in pulmonary vaculitides.

This study was performed to determine the value of transbronchial biopsy (TBB) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides and mild-to-moderate pulmonary involvement. Included in the study were 19 patients with Wegener's granulomatosis (WG) and six patients with Churg-Strauss syndrome (CSS) with evidence of active pulmonary disease but without gross parenchymal lesions accessible by radiologically guided biopsy. All of the patients had undergone staging examinations which included TBB taken from peripheral lung tissue and from any focal tracheobronchial lesions. Any suspicious lesion in the upper respiratory tract was biopsied by an otolaryngologist and the number of positive biopsies was compared with that of TBB. In the WG patients, only two out of 17 biopsies of alveolar tissue yielded histopathological findings supporting the diagnosis of WG. In five WG patients, ulcerative or exophytic airway lesions were found whose histopathologies were invariably positive. Otolaryngological examination revealed abnormal findings in 19 WG patients and biopsies from these sites yielded positive results in 13 instances. In CSS, TBB produced a diagnostically helpful histopathology in four of six cases and biopsies from the upper respiratory tract were positive in five out of six cases. We conclude that transbronchial biopsies of alveolar tissue are seldom positive in Wegener's granulomatosis patients with mild-to-moderate pulmonary disease unless they are taken from grossly abnormal lung areas. Conversely, ulcerative, exophytic or stenotic tracheobronchial lesions had a high rate of positive findings. These results further suggest that the upper rather than the lower respiratory tract should be the biopsy site of first choice in Wegener's granulomatosis. In Churg-Strauss syndrome, the upper and lower respiratory tract seem to yield a roughly equal number of positive biopsies.

Adult↗
PubMed1997

[Disturbed neutrophil activation in pneumonia during medicinal immunosuppression].

BACKGROUND: In medically immunosuppressed patients with pneumonia, the BAL cell differential and neutrophils secretion products were determined and compared to patients with pneumonia without defined immunodeficiency in order to define a possibly deficient neutrophil function. PATIENTS AND METHODS: Forty-eight medically immunosuppressed patients were studied: 24 pts. after renal transplantation receiving threefold immunosuppression (cyclosporine, azathioprine, prednisolone), 14 pts. with non-Hodgkin-lymphoma receiving polychemotherapy and 10 pts. with rheumatologic disorders (rheumatoid arthritis n = 3, M. Wegener n = 5 und SLE n = 2) receiving cyclophosphamide or methotrexate. For comparison, 116 patients without defined immunodeficiency and pneumonia and 16 healthy adults were studied. In addition to the cell differential the BALF concentrations of the neutrophil degranulation products myeloperoxidase (MPO) and lactoferrin were determined using immunoluminometric assays. For identification of microorganisms semiquantitative cultures were used. RESULTS: Neutrophilia > 5% in BAL was present in only 36% of the immunosuppressed pts. in contrast to 91.3% of the immunocompetent pts. (p < 0.01). The same pathogen was found in 14 pts. of each group, so that a pathogen matched comparison was possible. The neutrophil percentage and the BALF concentration of lactoferrin was significantly lower in the immunosuppressed group. In blood there was no difference with regard to the neutrophil count between the groups. CONCLUSIONS: BAL characteristics of immunosuppressed pts. are different from those of immunocompetent pts. with pneumonia. The pathogen-matched comparison proved that this is not due to different pathogens. Medically immunosuppressed patients with pneumonia exhibit a disturbed neutrophil recruitment. A neutrophil percentage < 5% in BAL of medically immunosuppressed patients does not preclude a bacterial infection.

Adult↗
PubMed1996

Admission levels of serum Gc-globulin: predictive value in fulminant hepatic failure.

Gc-globulin scavenges actin released from necrotic hepatocytes to the extracellular space. In 77 patients with fulminant hepatic failure (FHF) (excluding patients treated with liver transplantation), admission levels of serum Gc-globulin and degree of complexing with monomeric actin (complex ratio) were determined to evaluate their predictive values in relation to survival/nonsurvival. Gc-globulin levels were significantly reduced in 47 nonsurvivors, compared with 30 survivors (96 +/- 71 mg/L vs. 169 +/- 101 mg/L, P < .001), whereas the complex ratio in nonsurvivors did not differ significantly from that of survivors. Gc-globulin levels were significantly lower in 59 patients with non-acetaminophen-induced FHF, compared with 18 patients with acetaminophen-induced FHF (P < .01). Using a cutoff level of serum Gc-globulin of 100 mg/L, a lesser value correctly predicted nonsurvival in 79 percent of patients with non-acetaminophen-induced FHF, whereas a higher value predicted survival in 60 percent. In patients with acetaminophen-induced FHF, nonsurvival was correctly predicted in 100 percent of patients and survival in 53 percent. In comparison, the King's College Hospital (KCH) criteria correctly predicted nonsurvival and survival in 69 percent and 57 percent, respectively, of the same non-acetaminophen-induced FHF patients and in 60 percent and 38 percent, respectively, of the acetaminophen-induced FHF patients. Thus, in our study population, the predictive properties of Gc-globulin were in the same range as the KCH criteria. An advantage of Gc-globulin is that it gives an estimate of the outcome already on admission. Acute liver transplantation should be considered in FHF patients with Gc-globulin less than 100 mg/L.

Acetaminophen↗
PubMed1996

Sustained cough in methotrexate therapy for rheumatoid arthritis.

Sustained cough is a frequent complaint in methotrexate (MTX) treatment for rheumatoid arthritis and can be a symptom of incipient MTX-induced pneumonitis. This study was performed to characterize MTX-associated cough clinically and to clarify by which means this condition can be distinguished from incipient MTX pneumonitis. Three patients with MTX-induced pneumonitis and 10 patients with sustained cough unassociated with pneumonitis were examined clinically, by pulmonary function testing, and bronchoalveolar lavage (BAL). In MTX pneumonitis, cough was associated with progressive dyspnoea, constitutional symptoms, impaired pulmonary function, and interstitial infiltration of variable degree by chest X-ray. BAL cytology invariably showed lymphocytic alveolitis while transbronchial biopsy revealed active interstitial inflammation in only one patient. Ten patients had sustained, nonprogressive cough in the absence of constitutional symptoms, progressive dyspnoea and impaired pulmonary function. Neither X-ray nor BAL nor transbronchial biopsy revealed any evidence of interstitial lung disease. In the majority of these patients, cough abated with symptomatic treatment with or without temporary discontinuation of MTX. It is concluded that MTX-associated cough can be a reflection of isolated airway disease. Clinically, absence of constitutional symptoms, impaired pulmonary function, and interstitial infiltration on X-ray distinguished this condition from incipient MTX pneumonitis. Cough without pulmonary parenchymal involvement appears to result from an irritant effect of MTX on the airways.

Aged↗