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Biomedical subjects

K Wassermann

Publications and source records attributed to K Wassermann.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Unclear pulmonary infiltrates with eosinophilia, a problem of differential diagnosis]

Unclear pulmonary infiltrates with eosinophilia, a problem of differential diagnosis. HISTORY AND ADMISSION FINDINGS: A 60-year-old woman was admitted for the diagnosis of pulmonary infiltrates. A year before she had been exposed to tuberculosis when working as a doctor in Manila, the Philippines. Ten days before admission she had spent 10 days in Sao Paulo, Brazil. On admission she complained of fatigue, dry cough and nocturnal sweating. Her body temperature was 37.8; C. At auscultation of the chest fine rales were heard with diminished percussion sounds over both lungs. INVESTIGATIONS: The chest radiogram showed bilateral apical infiltrates. Blood count indicated normal white and red cells, but platelets were raised to 606 x 10 9/l. The differential blood count revealed an eosinophilia of 30%, ESR was raised at 91 mm/h and C-reactive protein increased to 103 mg/l. Angiotensin-converting enzyme, IgG, IgA, IgM, IgE, C3 and C4, paraproteins, antinuclear antibodies and double-strand DNA antibodies were all within normal limits. There was no direct or indirect evidence of tuberculosis and no parasites were found in sputum, stool, urine and blood. DIAGNOSIS, TREATMENT AND COURSE: After bronchoscopy with bronchial biopsy had failed to establish a diagnosis, an open lung biopsy with partial lung resection was performed. This revealed histologically an eosinophilic pneumonia with intra-alveolar protein precipitation and multinucleated giant cells, as well as interstitial fibroblast proliferation without demonstrable mincroorganisms. Under cortisone administration there was striking improvement of symptoms within a few days, and C-reactive proteins fell to 3 mg/l, ESR to 25 mm/h and the eosino-philia to 2%. CONCLUSION: Eosinophilic pneumonia should be included in the differential diagnosis of unclear pulmonary infiltrations with eosinophilia, once parasitological and malignant diseases, tuberculosis and allergic pulmonary aspergillosis have been excluded.

Journal Article↗
PubMed2000

Meiosis-activating sterol-mediated resumption of meiosis in mouse oocytes in vitro is influenced by protein synthesis inhibition and cholera toxin.

To explore the possible signaling pathways of meiosis-activating sterol (MAS)-induced oocyte maturation and to elucidate whether the MAS pathway involves transcription or translation, arrested immature mouse oocytes were cultured with either the protein synthesis inhibitor cycloheximide or the heteronuclear RNA inhibitors alpha-amanitin or actinomycin D, respectively. Moreover, the possible involvement of a G protein-coupled receptor mechanism in MAS-mediated oocyte maturation was explored by influencing oocyte maturation with cholera toxin (CT). MAS-induced oocyte maturation was completely blocked by the addition of 50 microg/ml cycloheximide 4 h before the addition of MAS. Simultaneous addition of MAS and the protein synthesis inhibitor also significantly reduced the meiotic resumption compared to that in MAS-treated controls. In contrast, neither of the treatment regimens to inhibit transcription of DNA to RNA was observed to have any effect on the MAS-induced resumption of meiosis. CT was observed to inhibit MAS-induced, but not spontaneous, oocyte maturation in vitro, suggesting a putative involvement of G protein-coupled receptor mechanism in the MAS mode of action. In conclusion, protein synthesis was found to be an essential requirement for maintaining the oocytes' responsiveness to MAS-induced resumption of meiosis, in contrast to transcription.

Amanitins↗
PubMed1999

[Stenoses of the upper airways. Lung function, local resistance and load compensation. A review].

In benign laryngotracheal stenosis the amount of respiratory deterioration rather than the crude morphologic appearance will determine whether or not surgical measures such as dilatation or resection should be applied. This review focuses on currently available and newly developed diagnostic tools to assess the functional importance of central airway obstruction. After an outline of upper airway physiology is formulated, spirometric measurements at rest are collected. Among these, Peak Expiratory Flow Rate (PEF) proved to be the simplest and most reliable parameter to monitor an obstructing lesion of the upper airways. A novel technique for fibrobronchoscopic assessment of glottic and tracheal resistance is presented in detail. In contrast to usual tests of total airflow resistance which cannot distinguish between central and peripheral contributions, this test identifies the pressure-flow-relationship created exclusively by the local lesion. In serial stenoses, it indicates which is of higher clinical impact. Patients with upper airway obstruction complain of impaired exercise capacity. They tend to hypoventilate with imminent respiratory muscle fatigue. Therefore, spiroergometry may play a role in defining the point of incomplete compensation of a central load. The decision to operate will depend upon up the degree of physical capacity required to compensate for the stenosis.

Airway Obstruction↗
PubMed1999

Measuring in situ central airway resistance in patients with laryngotracheal stenosis.

OBJECTIVES: To evaluate a newly developed bronchoscopic technique for the assessment of intratracheal pressures. STUDY DESIGN: In situ measurement of central airway resistance in 20 consecutive spontaneously breathing subjects. Thirteen patients had benign glottic or subglottic stenosis. Seven patients without central airway disease served as normal control subjects. METHODS: A pressure catheter was introduced into the trachea via the working channel. The pressure swing was measured upstream and downstream of the stenosis. Central airflow was monitored simultaneously using a commercial pneumotachograph attached to a mouthpiece. Data acquisition frequency was 500 Hz. Prestenotic and poststenotic inspiratory and expiratory resistances could be calculated and displayed from the raw data off-line. RESULTS: Inspiratory and expiratory resistances measured in mid-trachea or below the stenosis (subglottic) were 0.36 +/- 0.13 and 0.35 +/- 0.13 kPa.s/L for the control subjects (C), 1.11 +/- 0.47 and 0.65 +/- 0.26 kPa.s/L for patients who did not need to be operated on (NOOP), 7.11 +/- 7.19 and 3.35 +/- 2.25 kPa.s/L respectively for those who required surgical correction (OP). Supraglottic inspiratory and expiratory resistances for C were 0.22 +/- 0.09 and 0.25 +/- 0.06 kPa.s/L, for NOOP 0.15 +/- 0.10 and 0.14 +/- 0.11 kPa.s/L, and for OP 0.26 +/- 0.13 and 0.24 +/- 0.07 kPa.s/L respectively. The cut-off point for surgical correction was estimated to be > 2.5 kPa.s/L of inspiratory resistance. Concurrent expiratory values showed a considerable overlap between OP and NOOP. No correlation could be established between local resistance values and dyspnea score. CONCLUSIONS: In situ subglottic flow-pressure tracing in spontaneously breathing patients who present with benign obstruction of the upper airways is well tolerated and may help to identify patients who need surgical correction.

Adult↗
PubMed1998

Proficient deoxyribonucleic acid repair of methylation damage in hamster ERCC-gene mutants.

Three major pathways, nucleotide excision repair (NER), base excision repair (BER) and O6-methylguanine-DNA methyltransferase (MGMT), are responsible for the removal of most adducts to DNA and thus for the survival of cells influenced by deoxyribonucleic acid (DNA) adduct-forming chemicals. We have evaluated host cell reactivation and cell survival of wild type Chinese hamster ovary cells and of mutants in the NER-genes ERCC1, ERCC2, and ERCC4 after treatment with the methylating compounds dimethylsulfate and methylnitrosourea. No effect of the three genes could be demonstrated, i.e., survival and host cell reactivation after methylation damage in the mutants and the wild type cells were similar. Gene-specific repair experiments confirmed the proficient removal of methyl lesions. We conclude that the three nucleotide excision repair genes are immaterial to the repair of methylation damage. This suggests that NER does not play a role in the removal of methylation in mammalian cells and that BER and MGMT are responsible for the survival of such cells, when they are challenged with methylation of DNA.

Animals↗
PubMed1998

Chronic eosinophilic pneumonia with atypical radiographic presentation.

Chronic eosinophilic pneumonia (CEP) is a rare disease characterized by a progressive symptomatic deterioration of more than 1 month, pulmonary infiltrates with eosinophils, and a dramatic response to corticosteroid treatment. We describe a patient with CEP who presented with right upper lung infiltrates with evidence of cavitation.

Anti-Inflammatory Agents↗
PubMed1998

Emergency stenting of malignant obstruction of the upper airways: long-term follow-up with two types of silicone prostheses.

We report on 10 patients with severe malignant "mixed-type" obstruction of the proximal trachea or distal trachea plus both main stem bronchi. They had far-advanced inoperable tumors (esophageal cancer in 4 patients, lung cancer in 3, and recurrent laryngeal, uvular, and thyroid cancers in 1 each). Emergency treatment consisted of a dilating bougie maneuver followed by the insertion of a large one-way (4 patients) or Y-shaped (6) silicone prosthesis. Subsequent to the intervention, there was long-lasting clinical improvement. The median survival from stent insertion was 8 months for all patients irrespective of tumor type; it was 5 months for lung carcinoma patients and 8 months for those with esophageal cancer. The results are in accordance with those of other studies using different therapeutic modalities. Stent exchange proved necessary in 5 patients. The main reasons were continuing tumor growth beyond the proximal and distal boundaries and recurrent productive bronchial infection. Patients died of pneumonia (4 patients), pulmonary lymphangitic spread (1), heart failure (2, one of whom also had pneumonia), and fatal hemorrhage (1). As of December 1995, 3 patients were still alive, 2, 5, and 8 months after stent implantation. As evidenced by clinical efficacy and length of palliation, endoscopic placement of silicone-based one-way and bifurcated prostheses in far-advanced tumor of the central airways is technically feasible and ethically justifiable.

Aged↗
PubMed1997

[Cystic form of Pneumocystis carinii pneumonia].

BASIC PROBLEM AND OBJECTIVE: In rare instances Pneumocystis carinii pneumonia (PCP) can occur in a cystic form, characterized by an acute course. The correct diagnosis is often missed. An analysis of a large cohort of patients with PCP was undertaken to determine the incidence and clinical manifestations of this form of the disease. PATIENTS AND METHODS: Data on all HIV-positive patients on the hospital registry, hospitalized with the diagnosis of PCP between January 1988 and July 1996, were retrospectively analysed. To be included in the study, PCP had to have been confirmed microscopically on bronchial lavage or histologically by lung biopsy. The chest radiogram and (if available) computed tomogram of these patients were examined for possible cystic changes, and clinical as well as laboratory findings recorded. RESULTS: Five of 180 patients with PCP had cystic changes (2.8%). The interval between first symptoms and diagnosis ranged from 30 to 200 days (median: 32 days). All five patients (age: 24-49 years; all males) had a far advanced immunological disorder (median CD4 count: 10/microliter) and were in stage C3 (Centers for Disease Control). Three of the five patients had prophylactically inhaled pentamidine (300 mg/month). Bronchial lavage was false-negative in three of the five cases. One patient had a spontaneous pneumothorax. Lactate dehydrogenase levels were normal or only slightly elevated (207-417 U/l; median 305 U/l). Both the cavities and thin-walled cysts were demonstrated radiologically, but were more visible on CT than on the X-ray film. All patients responded well to the medication with cotrimoxazole, but the prognosis was poor with a survival time of only 0.3 to 16 months. CONCLUSION: PCP should be included in the differential diagnosis when HIV patients have cystic lung changes. Invasive diagnostic methods are often required to avoid wrong diagnosis and superfluous therapeutic interventions.

Adult↗
PubMed1997

Analysis of single and double-stained alveolar macrophages by flow cytometry.

The quantification of cell surface antigens on human alveolar macrophages using flow cytometry is complicated by strong autofluorescence which varies with cell size and granularity. We report here a new method for overcoming the analytical problems caused by autofluorescence. After positioning the unstained cells along the 0, 0; 10(4), 10(4) diagonal on all three fluorescence dot-plots (FL1 vs. FL2; FL2 vs. FL3; FL1 vs. FL3) of a single-laser flow cytometer (excitation wavelength at 488 nm) and adjusting compensation so that the reference FL3 channel profile is not changed by PE-staining, the cell population on the FL3 histogram is arbitrarily classified into subpopulations having similar autofluorescence intensity. These are subsequently back-gated onto the FL1 vs. FL2 dot-plot and separately analyzed. The percentage of stained cells in the whole population is then calculated on the basis of absolute numbers or as the weighted mean of all the subpopulations. This approach permits the analysis not only of single-stained but also double-stained human alveolar macrophages.

Antigens, Surface↗
PubMed1997

Nitrogen mustard-mediated mutagenesis in human T-lymphocytes in vitro.

The cytotoxic and mutagenic effect of the bifunctional alkylating agent nitrogen mustard (HN2) was examined. Primary human lymphocytes were exposed to graded doses of HN2 in vitro and relative survival was determined. Mutation induction at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus was measured by cloning the exposed T-cells in microtitre plates in the presence and absence of 6-thioguanine (TG). The IC50-value determined for 30 min exposure to HN2 was 1.34 microM. The mutant frequencies (MF) in exposed T-cell cultures were 10-fold (2 microM HN2) to 32-fold (4 microM HN2) higher than those of unexposed cultures (median values). Nitrogen mustard-mediated mutagenesis is discussed in terms of the current ideas about DNA damage and repair.

Cell Survival↗
PubMed1997

Clinical and laboratory evaluation of a new thin-walled self-expanding tracheobronchial silicone stent: progress and pitfalls.

BACKGROUND: Although widely established in the management of malignant airway lesions, currently available tracheobronchial prostheses made of silicone have their drawbacks resulting from rigidity and wall thickness. Therefore we present clinical follow-up data obtained with a novel thin-walled expandable prototype silicone airway stent (Polyflex stent, Willy Rüsch AG, Kernen, Germany) in 19 patients. METHODS: Seventeen of 19 patients had tracheobronchial complications of infiltrating cancer: five had respiratory-digestive fistulas, 14 had mixed-type obstructions (mucosal infiltration plus extrinsic compression), and two had diffuse tracheal hemorrhages from the tumor surface (three patients had more than one complication). Two of 19 patients had benign postintubation stricture and malacia. Overall, 33 stents were implanted either simultaneously or in a consecutive manner. Scanning electron microscopy was performed both on prototype stents and on other available silicone stents for comparison. RESULTS: The treatment improved the patients' clinical condition substantially. The mechanical properties of the new prosthesis were excellent. Important stent-associated side effects were early mucus retention (n = 7), infolding of the inner silicone layer (n = 2), and stent dislodgment (n = 2). As of February 1997, 10 patients have died of causes unrelated to stent placement. Seven patients with malignant airway disease are still alive from 2 weeks up to 7 months after initial treatment. Scanning electron microscopy of explanted and unused prototypes suggested that an extremely ragged luminal microstructure may contribute to the firm adhesion of secretory material and that technical smoothing of the surface avoids such complications. CONCLUSIONS: The novel self-expandable silicone airway stent may be a promising addition to commonly used stent types. Short-term and medium-term management of fistulas, tumor surface bleeding, and strictures (malignant and benign) is satisfactory. Scanning electron microscopy of stents provides information on peculiar features of microstructure and material that may be of use in clinical research and technical innovation.

Adult↗
PubMed1997

[Value of polymerase chain reaction (PCR) in diagnosis of tuberculosis and mycobacterium infections caused by ubiquitous mycobacteria].

The rise in both incidence and the number of multi-drug-resistant strains has made tuberculosis an alarming health problem even in some developed countries. Moreover, due to the HIV pandemic an increase in mycobacterial diseases caused by ubiquitous mycobacteria has been observed. The microbiological standard procedures are critical diagnostic tools, and a more rapid detection of mycobacteria by new laboratory techniques would be helpful. We investigated the role of the polymerase chain reaction (PCR) in the detection of M. tuberculosis complex and of ubiquitous mycobacteria. 580 clinical specimens obtained from 525 patients were examined. The majority of sampled material was bronchoalveolar lavage fluid. Based on cultural identification of mycobacteria, the incidence of tuberculosis in our patients was 3.4%. For detection of M. tuberculosis complex the insertion sequence IS 6110 was used. Relative to cultural identification, diagnostic specificity of PCR was 99.5%, and sensitivity was 66.7%, respectively. In 3.0% of the total patient group and in 8.8% of HIV-infected patients an infection by ubiquitous mycobacteria was found. Ubiquitous mycobacteria were detected using the hypervariable region of the 16S-rRNA-gene, and species-identification was done by sequence analysis. For ubiquitous mycobacteria, sensitivity of PCR was 60.0% relative to cultural identification and 62.5% relative to a proven disease. PCR is a useful method in the rapid diagnosis of pulmonary tuberculosis with excellent specificity but lack of sensitivity.

AIDS-Related Opportunistic Infections↗
PubMed1997

[Evaluation of the validity of spiroergometric parameters in the differentiation of circulatory and ventilatory physical limitation].

BACKGROUND: One of the indications postulated for cardiopulmonary exercise testing (CPX) is the distinction between ventilatory and cardiocirculatory reasons of an exercise limitation. Though data such as anaerobic threshold, breathing- and heart-rate-reserve, difference of arterial and alveolar oxygen pressure, ratio of ventilation to O2 and CO2 output and aerobic capacity are commonly considered in CPX interpretation, exact choice of parameters and cut-off-points is not definitely clear. The aim of our study therefore was to scrutinize the validity of these parameters and the recommended cut-off-points. A second goal was to evaluate the reliability of a standardized CPX interpretation as postulated by Wassermann and Palange. PATIENTS AND METHODS: We examined 19 patients with congestive or ischemic cardiomyopathy, 24 subjects with chronic obstructive or interstitial lung disease (n = 11 resp. n = 13). The control group consisted of 15 healthy people. During incremental cycle exercise we measured the ventilatory frequency, the peak O2 uptake and the oxygen pulse as well as the above mentioned parameters. Data were interpreted according to Wassermann and Palange in order to confirm the diagnosis of a cardiocirculatory or ventilatory conditioned exercise limitation. Additionally we determined the cut-off-points with the highest diagnostic value for our patient groups. RESULTS: According to Palange only 7% of the diagnosis could be confirmed, 55% were correctly ascertained by data interpretation according to Wassermann. Breathing reserve (45% of maximum voluntary ventilation) proved to be the only parameter with satisfying selectivity (sensitivity = 75%; specificity = 95%). Diagnostic value of all other recorded data was worse by far. CONCLUSIONS: Our study shows that standardized interpretation of CPX data does not lead to the correct diagnosis in a satisfying percentage. In any case results have to be confirmed by conventional tests such as ECG or spirometry, so that the additional diagnostic value of CPX in patients with an exercise limitation of unknown origin has to be seen very critically. Except breathing reserve from our point of view there is still no valid parameter or cut-off-point to distinct cardiocirculatory from ventilatory exercise limitation that can be recommended.

Adult↗
PubMed1996

Ongoing activity of RNA polymerase II precludes chromatin collapse and DNA fragmentation in Chinese hamster ovary cells.

The role of ongoing RNA synthesis in chromatin organization in Chinese hamster ovary cells was examined upon exposure to the transcription inhibitor alpha-amanitin. Treatment with alpha-amanitin led to pleomorphic nuclei with chromatin heavily condensed and with the remaining ribonucleoprotein aggregated in large compact granular masses around the margins of the nuclear periphery. Concommitant with the changes in nuclei morphology transient focal dilatation of the rough endoplasmic reticulum was observed while other cytoplasmic organelles appeared structurally unaffected. The morphological changes occurred after complete inhibition of RNA polymerase II mediated transcription. The molecular integrity of isolated DNA was monitored in parallel with the structural analysis. Fragmentation of cellular DNA occurred in a time-dependent fashion and well after the complete inhibition of RNA synthesis. Characteristic oligonucleosomesized DNA fragments of about 187 base pairs in length was produced in a cotemporal time-dependent fashion. Our findings indicate that ongoing transcription and the structural state of chromatin are very closely integrated, and provide further evidence that RNA is a structural component of the nuclear matrix, which in turn is involved in keeping chromatin physically dispersed and decondensed.

Amanitins↗
PubMed1996

Emergency stenting of malignant obstruction of the upper airways: long-term follow-up with two types of silicone prostheses.

OBJECTIVE: We evaluated the long-term prognosis of stents placed on an emergency basis in the trachea and its bifurcation for malignant stenosis. METHODS: We retrospectively analyzed all bronchologic treatments of obstructing airway lesions from January 1993 to December 1995. RESULTS: We report on 10 patients with severe malignant "mixed-type" obstruction of the proximal trachea or distal trachea plus both main-stem bronchi. They had far-advanced inoperable tumor (esophageal cancer: n = 4; lung cancer: n = 3; recurrent laryngeal, uvula, and thyroid cancer: n = 1 each). Emergency treatment consisted of a dilating bougie maneuver followed by the insertion of a large one-way (n = 4) or Y-shaped silicone prosthesis (n = 6). After the intervention, there was a long-lasting clinical improvement. Median survival from stent insertion was 8 months for all patients irrespective of tumor type; it was 5 months for patients with lung carcinoma and 8 months for those with esophageal cancer. The results are in accordance with other studies using different therapeutic modalities. Stent exchange was necessary in five patients. Main reasons were continuing tumor growth beyond the proximal and distal boundaries and recurrent productive bronchial infection. Patients died of pneumonia (n = 4), pulmonary lymphatic spread (n = 1), cardiac failure (n = 2), and fatal hemorrhage (n = 1). As of December 1995, three patients were still alive 2, 5, and 8 months after implantation. CONCLUSIONS: As evidenced by clinical efficiency and length of palliation, endoscopic placement of silicone-based one-way and bifurcational prostheses in far-advanced tumor of the central airways is technically feasible and ethically justifiable.

Aged↗
PubMed1996

Somatic mutation detection in human biomonitoring.

Somatic cell gene mutation arising in vivo may be considered to be a biomarker for genotoxicity. Assays detecting mutations of the haemoglobin and glycophorin A genes in red blood cells and of the hypoxanthine-guanine phosphoribosyltransferase and human leucocyte antigenes in T-lymphocytes are available in humans. This MiniReview describes these assays and their application to studies of individuals exposed to genotoxic agents. Moreover, with the implementation of techniques of molecular biology mutation spectra can now be defined in addition to the quantitation of in vivo mutant frequencies. We describe current screening methods for unknown mutations, including the denaturing gradient gel electrophoresis, single strand conformation polymorphism analysis, heteroduplex analysis, chemical modification techniques and enzymatic cleavage methods. The advantage of mutation detection as a biomarker is that it integrates exposure and sensitivity in one measurement. With the analysis of mutation spectra it may thus be possible to identify the causative genotoxic agent.

Environmental Monitoring↗