Search PubMed⌕ Search

Biomedical subjects

R Haupt

Publications and source records attributed to R Haupt.

At least 37 records · Page 2Linked to original sources
PubMed2001

Interferon gamma and tumour necrosis factor alpha are overexpressed in bone marrow T lymphocytes from paediatric patients with aplastic anaemia.

Twelve paediatric patients with aplastic anaemia and two groups of normal control subjects underwent flow cytometric analysis for intracytoplasmic expression of gamma interferon (gamma-IFN) and tumour necrosis factor alpha (TNF-alpha) in bone marrow and peripheral blood CD4+ and CD8+ cells. The same cytokines were tested, by immunoassay, in culture supernatants from unstimulated bone marrow mononuclear cells (MNCs). Marrow CD4+ and CD8+ cells expressing gamma-IFN and TNF-alpha were significantly increased in the patients in comparison with normal control subjects (P from < 0.05 to < 0.0001 in the different cellular subsets). Patients' marrow CD4+ and CD8+ cells containing gamma-IFN and TNF-alpha were significantly increased when compared with the same cell fractions from paired peripheral blood samples (P from < 0.05 to < 0.0001 in the various cellular subsets). In the supernatant of marrow MNCs, gamma-IFN and TNF-alpha were detected in four out of eight and five out of eight cases, respectively, whereas neither cytokine was traceable in the control subjects. Patients' peripheral blood CD4+ and CD8+ cells containing gamma-IFN and TNF-alpha were not significantly increased in comparison with those from normal control subjects. Whereas patients with favourable and unfavourable outcomes had no significantly different proportions of marrow gamma-IFN+/CD4+ and gamma-IFN+/CD8+ cells, the percentages of marrow CD4+ and CD8+ cells containing TNF-alpha were significantly lower in subjects with favourable than in those with unfavourable outcome. Overall, these findings show that, in aplastic patients, T cells overexpressing gamma-IFN and TNF-alpha concentrate in the bone marrow and that intracytoplasmic expression of TNF-alpha in marrow CD4+ and CD8+ cells is associated with an unfavourable clinical course.

Adolescent↗
PubMed2000

Early and late deaths after elective end of therapies for childhood cancer in Italy.

The first cohort of subjects treated for cancer during childhood is now entering adulthood, and it is necessary to determine whether treatment has been sufficient to completely eradicate the neoplastic clone, and whether the cancer itself or treatment-related toxicity may have increased the risk of premature death. For these reasons, long-term survival and causes of death were evaluated in a cohort of subjects treated for childhood cancer who reached the elective end of therapy in continuous remission and were registered until 1992 in the Italian Registry of off-therapy subjects (OTR). The vital status of OTR subjects was ascertained in 1996 by a postal survey through census bureaux; for deceased subjects, the cause of death was defined and compared with the expected rates in the general population. At follow-up, out of 6402 eligible and evaluable subjects, 890 were found to have died; the estimated overall survival at 20 years was 80.7% (95% CI 79.3-82.1). Most of the patients (84.6%) died due to recurrence of the primary cancer, usually within the first 5 years after the OT. The cumulative incidence of death due to recurrence of the primary tumor was greater among subjects treated for solid tumor than among those treated for leukemia/lymphoma (p = 0.0001); in contrast, OT subjects after leukemia and lymphoma were more likely to die due to of medical complications of therapy (p < 0.02). Second cancers were the second most frequent cause of death, with a 12-fold risk compared with the general population; the figures were similar in the 2 cancer groups. Compared with the general population, OT subjects were 32 times more likely than same-age subjects to die. The SMR decreased to 6.1 when only non-cancer deaths were considered. Deaths due to external or avoidable causes occurred among survivors at a rate similar to that of the general population.

Adolescent↗
PubMed2000

Angiomatoid (malignant) fibrous histiocytoma as a second tumour in a child with neuroblastoma.

Neuroblastoma occurring as a disseminated disease in children has a poor prognosis. Haematogenous metastases usually involve the marrow, bone, liver and skin. A second neoplasm may also develop. We describe a child with retroperitoneal neuroblastoma (stage 3) who developed a nodular mass in the inguinal area which was suspected to be a metastasis. Histopathology disclosed an angiomatoid (malignant) fibrous histiocytoma, and excision was curative. The occurrence of angiomatoid (malignant) fibrous histiocytoma as a second tumour in a patient with neuroblastoma has not previously been reported.

Abdominal Neoplasms↗
PubMed2000

Preterm infants with high polyunsaturated fatty acid and plasmalogen content in tracheal aspirates develop bronchopulmonary dysplasia less often.

OBJECTIVE: Oxygen toxicity causes chronic bronchopulmonary dysplasia (BPD) in extremely preterm infants. Polyunsaturated fatty acids (PUFA) and plasmalogens are the two main substrates for lipid peroxidation in the pulmonary surfactant. In the present study, we tested whether low concentrations of both were associated with development of BPD and whether both were further reduced during mechanical ventilation with oxygen. DESIGN: Prospective, noninterventional, descriptive study. SETTING: Level III neonatal intensive care unit in a university hospital. PATIENTS: In 25 extremely low birth weight infants with respiratory distress syndrome, tracheal aspirates were collected immediately after birth and in the following 4 days. As control, tracheal and pharyngeal aspirates were collected from healthy infants immediately after birth. The amount of PUFA and dimethylacetals (DMA, representing plasmalogens) was determined gas-chromatographically. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The relative percentages of PUFA and DMA on all fatty acids in non-BPD infants (PUFA% 26+/-8.9, DMA% 3.5+/-1.2) were higher compared with infants who developed BPD (PUFA% 14.5+/-3.8, DMA% 1.8+/-0.9). In term healthy infants, DMA% and PUFA% were in the same range as in the BPD group. The higher levels found for non-BPD infants decreased after day 1 to values equal to the BPD group and remained low. CONCLUSIONS: The results suggest that initially higher levels of PUFA and plasmalogens in the tracheal effluent are associated with a reduced risk of developing BPD and are reduced during the first day of ventilation.

Bronchopulmonary Dysplasia↗
PubMed2000

Increase in fragmented phosphatidylcholine in blood plasma by oxidative stress.

Oxidatively modified phospholipids with fragmented acyl chains have attracted much interest because of their proinflammatory activity and their potential involvement in atherosclerosis. They can be formed in vitro by free radical treatment of unsaturated phospholipids but it is not known under which conditions they accumulate in vivo. We assayed one species of fragmented phosphatidylcholine (PC) in human blood plasma by high performance liquid chromatography after precolumn derivatization with chloromethylanthracene. Structural analysis suggested that fragmented PC was a diacyl species with a palmitoyl group and a short oxidized residue, which most likely had four carbons. The concentration of fragmented PC was higher in elderly individuals with coronary heart disease than in young healthy controls. Smoking one cigarette acutely increased the concentration of fragmented PC in healthy adults. Fragmented PC also increased in the reperfusion period after treatment with cardiopulmonary bypass. The increase coincided with a surge of circulating neutrophils. In rats, the plasma concentration of fragmented PC was elevated by vitamin E deficiency and exposure to high oxygen. The data demonstrate that fragmented PC increases in blood plasma in response to various forms of oxidative stress.

Adult↗
PubMed1999

Metastasizing signet ring cell carcinoma of the stomach-mimicking bilateral inflammatory breast cancer.

We describe a case of unusual metastases of a gastric carcinoma to the female breast, there likely to be an inflammatory breast cancer. A 46-year-old woman was admitted to our institution with bilateral breast tumors, not typical for a breast cancer as tumor growth was synchronically bilateral within a very short period of only 2 months. The woman underwent a palliative gastrectomy 3 months before for a poorly differentiated adenocarcinoma with signet ring appearance presenting as linitis plastica. At the time of the first operation the mammary glands were not suspicious. Breast biopsies assured metastases of the gastric cancer. In addition to this case report, a short overview of the literature concerning the very few cases of metastases of gastric cancer to the breast is given.

Breast Neoplasms↗
PubMed1999

Familial clustering of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is considered a non-hereditary disorder. Evaluation of the few familial cases might provide insight into its aetiology and pathogenesis. We conducted a survey to identify familial LCH cases. Data on family history, zygosity assessment in twins, clinical and laboratory features, treatment outcome, and present status were collected. According to variable confidence for twins monozygosity assessment, we termed these pairs 'presumed monozygotic' (pMZ). Nine families had more than one affected relative: five with LCH-concordant twin pairs, four with LCH in siblings or cousins. Three twin pairs not concordant for LCH were also studied. Overall, four of five pMZ twin pairs and one of three dizygotic (DZ) pairs were concordant for LCH. The pMZ twins had simultaneous and early disease onset (mean age 5.4 months); onset was at 21 months in the DZ pair. Clinical features were similar in the pMZ pairs. One pair of DZ twins had disseminated LCH. The three healthy twins (one pMZ, two DZ) remain asymptomatic 0.3, 5.9 and 4.7 years, respectively, after disease onset in their co-twins. Of the two families with affected non-twin siblings, one had known parental consanguinity and the other possible consanguinity. Potential consanguinity was also present in one of the two families with affected first cousins. Our data support high LCH concordance rates in pMZ twins and add the finding of LCH concordance in one of three dizygotic pairs studied. Taken together with our identification of LCH in siblings and first cousins from known or possibly consanguineous families, and with prior reports of three affected parent-child pairs, the data support a role for genetic factor(s) in LCH. The work-up of newly diagnosed patients should include a careful, extensive family history and chromosome studies. When possible, constitutional and/or lesional DNA should be obtained for future study.

Child, Preschool↗
PubMed1999

Fatty acid translocase/CD36 mediates the uptake of palmitate by type II pneumocytes.

Type II pneumocytes, which synthesize, store, and secrete pulmonary surfactant, require exogenous fatty acids, in particular palmitic acid, for maximum surfactant synthesis. The uptake of palmitate by type II pneumocytes is thought to be protein mediated, but the protein involved has not been characterized. Here we show by RT-PCR and Northern blot analysis that rat type II pneumocytes express the mRNA for fatty acid translocase (FAT/CD36), a membrane-associated protein that is known to facilitate the uptake of fatty acids into adipocytes. The deduced amino acid sequence from rat type II pneumocytes reveals 98% identity to the FAT/CD36 sequence obtained from rat adipocytes. The uptake of palmitate by type II pneumocytes follows Michaelis-Menten kinetics (Michaelis-Menten constant = 11.9 +/- 1.8 nM; maximum velocity = 62.7 +/- 5.8 pmol. min(-1). 5 x 10(5) pneumocytes(-1)) and decreases reversibly under conditions of ATP depletion to 35% of control uptake. Incubation of cells at 0 degrees C inhibited the uptake of palmitate almost completely, whereas depletion of potassium was without effect. Preincubation of the cells with bromobimane or phloretin decreases the uptake of palmitate significantly as does preincubation with sulfo-N-succinimidyl oleate, the specific inhibitor of FAT/CD36 (C. M. Harmon, P. Luce, A. H. Beth, and N. A. Abumrad. J. Membr. Biol. 121: 261-268, 1991). From these data, we conclude that FAT/CD36 is expressed in type II pneumocytes and mediates the uptake of palmitate in a saturable and energy-dependent manner. The data suggest that the uptake process is independent of the formation of coated pits and endocytotic vesicles.

Amino Acid Sequence↗
PubMed1998

Development of pulmonary lipophilic antioxidants and peroxidizable lipids during lung maturation.

The objective of this article is to test whether the concentration of potentially oxidizable lipids (polyunsaturated fatty acids [PUFA], total and free cholesterol) and lipophilic antioxidants (plasmalogens, vitamin E) in the fetal lung correlate with lung maturation (P/S ratio). In amniotic fluid palmitic/stearic acid (P/S) ratio, concentrations of PUFA, total and free cholesterol, vitamin E, and plasmalogens were measured. Ratio of PUFA to stearic acid (PUFA/S ratio) was determined in lung effluent of 15 preterm infants with IRDS and compared with values from 15 term healthy infants. Concentrations of plasmalogens, PUFA, total and free cholesterol increase significantly with increasing P/S ratio. No correlation of vitamin E with lung maturation has been found. The PUFA/S ratio is significantly lower in lung effluent of preterm (0.79 +/- 0.27) when compared with term infants (2.02 +/- 0.38). Our results suggest that the higher susceptibility of preterm infants for oxidative lung injury is not caused by an unfavorable ratio of oxidizable lipids to lipophilic antioxidants in surfactant, but rather by a lower amount of PUFA containing surfactant lipids. Our results are in accordance with data from Sosenko et al. who have shown that high levels of PUFA in the rat lung have a protective effect against oxygen-induced lung damage.

Amniotic Fluid↗
PubMed1998

Study of platelet-activating factor acetylhydrolase in the perioperative period of patients undergoing cardiac surgery.

After operations with cardiopulmonary bypass, patients often show early symptoms of the systemic inflammatory response syndrome (SIRS). Potential mediators of SIRS include the platelet-activating factor (PAF), which has been linked to septic shock and multiple organ dysfunction. We studied the effect of cardiac surgery on PAF acetylhydrolase, the PAF-degrading plasma enzyme, as well as the relationship between the enzyme and the postoperative state of the patients. PAF acetylhydrolase activity decreased by 38+/-8% after instituting cardiopulmonary bypass because of plasma dilution and returned to near-preoperative levels within 6 h postsurgery. After that, enzyme levels decreased again, resulting in a 24+/-12% reduction until at least 3 days postsurgery. Patients in poor postoperative condition (Acute Physiology Score >9) had a lower preoperative PAF acetylhydrolase activity than did normal patients (12+/-4 vs. 17+/-4 nmol min(-1) mL(-1); p < .05). Likewise, patients who developed postoperative SIRS had a lower preoperative PAF acetylhydrolase activity than did patients without SIRS (12+/-3 vs. 17+/-4 nmol min(-1) mL(-1); p < .05). The data suggest that PAF acetylhydrolase deficiency is among the factors associated with postoperative distress after cardiac surgery.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1998

Are biochemical parameters of lung maturation from gastric, tracheal, and pharyngeal aspirates comparable?

Phospholipid parameters -- lecithin/sphingomyelin (L/S) ratio and palmitic acid/stearic acid (P/S) ratio -- of gastric (GA), pharyngeal (PA), and tracheal aspirates (TA) have often been used for estimation of lung maturation. However, it was not known whether values from different sources can be alternatively used. The study was performed to test whether P/S and L/S ratios in GA, PA, and TA are comparable. 11 GA, 30 PA, and 10 TA were obtained from infants within 10 min after birth. All infants were healthy, vaginally delivered with no respiratory distress, and had a gestational age > or = 34 weeks. Patterns of fatty acids were determined by gas chromatography and the L/S ratio by high-performance liquid chromatography. We found lower L/S ratios in GA (16.5 +/- 5.2) when compared with PA(39 +/- 16) or TA (41 +/- 15; p < 0.01); there were no differences between PA and TA. The P/S ratio was in the same range in PA and TA, but lower in GA. As compared with TA and PA, in GA the relative percentage of palmitic acid of all fatty acids was lower, the percentage of monounsaturated fatty acids, however, higher. We conclude that phospholipid parameters of lung maturation in PA and TA, but not in GA, can be alternatively used.

Gastric Juice↗
PubMed1998

[Successful therapy of pulmonary aspergillosis in a patient with non-Hodgkin lymphoma].

UNLABELLED: ANAMNESIS AND CLINICAL PICTURE: A 65-year old male with non-Hodgkin lymphoma developed severe invasive pulmonary aspergillosis during a state of leucopenia after chemotherapy. INVESTIGATION: The initial manifestation was an infiltration in the right upper lobe of the lung, identified by lung scintigraphy as a peripheral wedge-shaped loss of perfusion. Both serum and bronchoalveolar lavage extreme high titre of Aspergillus antigen were seen as a laboratory indication of an invasive aspergillosis. The mould Aspergillus fumigatus was repeatedly isolated from bronchoalveolar lavage and bronchial secretion. THERAPY AND CLINICAL COURSE: Treatment was started with amphotericin B plus 5-flucytosine together with repeatedly bronchoscopic instillation of miconazole followed by thoracosurgical intervention with resection of the right upper lobe of the lung. Despite prophylaxis by itraconazole, a relapse of invasive aspergillosis occurred three months later probably due to persistence of aspergillus fungal elements in the left lung. The aspergillosis relapse was treated at first with liposomal amphotericin B. After eighteen days of treatment this was changed to a combination of 5-flucytosine with oral application of itraconazole, and cure was achieved.

Aged↗
PubMed1997

Risk of secondary leukemia after treatment with etoposide (VP-16) for Langerhans' cell histiocytosis in Italian and Austrian-German populations.

To estimate the risk of secondary leukemias after treatment with etoposide (VP-16), we evaluated subjects treated for Langerhans' cell histiocytosis (LCH) according to cooperative protocols in Italy or in Austria, Germany, Holland and Switzerland (AGDS). For each subject, information was collected on the cumulative dosages of chemotherapy and radiotherapy received, vital status and occurrence of secondary leukemia. The expected number of leukemias was estimated using age-specific incidence rates from the cancer registries in Italy and Germany. Standardized incidence ratios (SIR) were used to measure the risk of secondary leukemia among LCH patients. Five leukemias occurred among the 241 Italian study patients (SIR 520), whereas no cases were reported among the 363 AGDS patients. Interestingly, and in contrast to previous descriptions of epipodophyllotoxin-related leukemias which are mostly FAB M4 or M5, these leukemias showed typical FAB M3 features, and received a dose of VP-16 > 4,000 mg/m2. Among the AGDS cohort, very few subjects were exposed to high doses of VP-16. The risk of secondary acute non-lymphoblastic leukemia (s-ANLL) among the Italian subjects exposed to VP-16 was more than 1,000 times greater than expected. The study suggests that high doses of VP-16 appear to increase the risk of s-ANLL in LCH patients. The fact that all the leukemias described in the Italian LCH cohort were promyelocytic, and evidence of a higher incidence of promyelocytic leukemias among Italians and Latinos, suggest that high doses of etoposide in subjects of Latino origin may lead to aberrations on chromosomes 15 and 17.

Adolescent↗
PubMed1996

Can protocol-specified doses of chemotherapy and radiotherapy be used as a measure of treatment actually received? A CCG/NIH study on long-term survivors of acute lymphocytic leukemia.

In a cohort of 593 long-term survivors of acute lymphocytic leukemia identified through the Children's Cancer Group (CCG), treatment abstracts were obtained and compared to protocol information on radiation therapy and intravenous chemotherapy. This was done in order to evaluate the actual compliance to protocol-specified treatment, and assess if protocol-specified doses can be used in studies of late effects of treatment. The compliance to protocol-specified type of treatment ranged between 95.3% (intrathecal methotrexate) and 98.6% (adriamycin) for chemotherapy, and between 94.1% (cranial radiation) and 97.0% (extended field radiation) for radiation. Concordance with the protocol-specified chemotherapy dose (+/- 25%) was 57.5% for adriamycin, 91.3% for daunomycin, and 48.5% for cyclophosphamide. When concordance was low, most patients received doses that were lower than expected. Concordance with chemotherapy was significantly lower for high-dose regimens than for low-dose regimens. Concordance with protocol-specified radiation dose (+/- 10%) was 87.4% for cranial radiation, 87.8% for spinal radiation, and 85.7% for extended field radiation. Concordance with treatment did not differ by gender, relapse status, or age at diagnosis. In this cohort of leukemia survivors, the validity of type of treatment was greater than the validity of dosage. Great care should be used when drawing conclusions about effects of treatment dosage. Although costly and time consuming, it appears that chart reviews are the most appropriate way to collect information about dose-related effects of therapy.

Adolescent↗
PubMed1996

Identification of short-chain oxidized phosphatidylcholine in human plasma.

Oxidized phospholipids have been recognized as potentially important compounds that carry biological activities similar to the platelet-activating factor, but their presence in biological tissue has not been firmly established. We developed a novel technique for the quantitative analysis of phospholipids with oxidized acyl chains. The method involves 1) lipid extraction, 2) chromatographic enrichment of phospholipids with short acyl chains, 3) derivatization with 9-(chloromethyl)anthracene, 4) solid-phase extraction of the derivatives, and 5) reversed-phase HPLC with fluorescence detection. The technique was capable of measuring dicarboxylate-containing phosphatidylcholines (PCs) at the picomole level. The method was suited to monitor the generation of oxidized phospholipids from 1-palmitoyl-2-arachidonoyl-PC in the presence of Fe21/ascorbate. The new procedure was used to isolate lipids from human plasma that were identified as anthracene derivatives of short-chain oxidized PC on the basis of chromatographic enzymatic, and spectroscopic evidence. The plasma concentration, determined with an internal standard (1-palmitoyl-2-suberoyl-PC), was 0.6 +/- 0.2 microM (n = 11). The analytical method did not produce oxidation antifacts in significant amount. We concluded that human blood contains oxidatively fragmented PC in submicromolar concentration.

Chromatography, High Pressure Liquid↗