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Biomedical subjects

J Hasse

Publications and source records attributed to J Hasse.

At least 37 records · Page 2Linked to original sources
PubMed1998

Antibacterial activity of human pleural fluid: alone and in combination with antibiotics.

This study investigated the antibacterial activity of human pleural fluid (HPF) and its interaction with gentamicin (GM), meropenem (MRPM), ciprofloxacin (CPFX) and clarithromycin (CLTM) against Escherichia coli K-12, Proteus rettgeri (Sanelli) and Staphylococcus aureus. Minimal inhibitory concentrations or volumes, expressed as MIC or volume percentage (MIV, V/V%), were measured using a micro-dilution technique in microtiter plates. The antimicrobial activity of HPF combinations with antimicrobial drugs was evaluated by the chequerboard method calculating the fractional inhibitory concentration index (FIC) values. HPF MIVs (%) were: 37.54; 19.85; 1.74 for E. coli, P. rettgeri and S. aureus, respectively. FIC values indicated a synergistic effect with GM, MRPM and CPFX against E. coli and P. rettgeri and an additive effect for the combination HPF plus CLTM or indifference with HPF plus GM and CPFX against S. aureus. The presence of antibodies, complement factors, lysozyme, alpha-defensins and enzymes could explain the antimicrobial activity of HPF and its synergistic effect with certain antibiotics.

Aged↗
PubMed1998

Results after surgery in stage-I bronchogenic carcinoma.

BACKGROUND: The aim of this retrospective study was to evaluate prognostic factors for recurrence-free survival in stage-I non-small-cell bronchogenic carcinoma. METHODS: During 9 years, 338 consecutive patients were operated on for stage-I bronchogenic carcinoma. Patients with small-cell carcinoma (n = 14), prior malignancies in locations other than pulmonary (n = 41), and patients with incomplete data on prognostic factors (n = 11) were excluded. Of the remaining 272 patients 226 were men. Mean age was 63 years (40 to 81 years). The resections performed comprised 215 lobectomies and bilobectomies, 36 segmentectomies and wedge resections, and 21 pneumonectomies. According to the number of sites of dissected lymph nodes 3 subgroups were formed: group A with 0 to 4 (n = 71), B with 5 to 6 (n = 118), and C with 7 to 10 sites (n = 83). Median follow-up was 46 months. RESULTS: Three patients (1.1 %) died within 30 days of operation. In 3 patients the resection was revealed to be not radical (R1). At the end of follow-up, 191 patients were alive, 174 of these without recurrence. Eighty-one patients had died, 53 associated with tumor recurrence. Four patients had died of non-pulmonary malignancies. Twenty-two patients died of causes not related to tumor disease. In 2 patients the cause of death could not be determined retrospectively. Overall 5-year survival was 65% (95% confidence interval [CI] 58-72%), recurrence-free survival 59% (CI 51-66%). Significant prognostic factors for recurrence-free survival were T stage (relative risk [RR] 1.7 for T2 vs. T1, CI 1.0-3.0), age (RR 1.9 for >70 years vs. < or =70 years, CI 1.1-3.1), adeno cell type (RR 2.3 vs. squamous cell, CI 1.4-4.0), as well as lymphangiosis carcinomatosa (RR 2.3, CI 1.2-4.4). Extent of operative resection, extent of lymphadenectomy, and sex did not influence survival. CONCLUSION: 5-year survival of our patients was in the range reported in literature. Most patients died of distant metastases. Our retrospective study probably underestimated the occurrence of second primary cancers of the lung. Limited resection in poor-risk patients showed equivalent results to lobectomy. The extent of lymph-node resections had no influence on survival of stage-I patients, however, it must be remembered that positive results in lymph nodes shift patients to higher stages.

Carcinoma, Bronchogenic↗
PubMed1998

Multimodality treatment including early high-dose chemotherapy with peripheral blood stem cell transplantation in limited-disease small cell lung cancer.

Combined-modality treatment for limited-disease small cell lung cancer using conventional chemotherapy and chest irradiation achieves high response rates, but most patients relapse over a period of 12 to 16 months. To improve current results, we performed a phase II trial including high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT) as part of an early intensification strategy after two cycles of induction therapy. Moreover, to reduce the risk of local recurrence, the protocol included surgical resection in stages I to IIIA patients as well as chest irradiation. Between January 1991 and July 1994, 16 consecutive patients (median age, 50 years; age range, 30 to 59 years) were treated in this single-center trial. The patients received two cycles of conventional chemotherapy consisting of etoposide 500 mg/m2, ifosfamide 4 g/m2, cisplatin 50 mg/m2, and epirubicin 50 mg/m2 plus granulocyte colony-stimulating factor 5 microg/kg at a 3-week interval, followed by PBPC collection and subsequent high-dose etoposide 1,500 mg/m2, ifosfamide 12 g/m2, carboplatin 750 mg/m2, and epirubicin 150 mg/m2 with PBPCT. The duration of the entire chemotherapy program was 9 weeks. Six of 10 patients in stages I to IIIA and one of six patients in stage IIIB received neoadjuvant or adjuvant surgery before high-dose chemotherapy, followed by thoracic (50 Gy) and prophylactic (30 Gy) cranial irradiation. Hematopoietic reconstitution after high-dose chemotherapy occurred within 11 days (range, 9 to 17 days) for both neutrophils (>0.5 x 10(9)/L) and platelets (>20 x 10(9)/L). Oral mucositis (World Health Organization grade 2 to 4) was the predominant nonhematologic toxicity, which was observed in 12 of 16 patients. One patient developed neutropenic septicemia with fatal multiorgan failure. At a median follow-up of 44 months (range, 32 to 77 months) after PBPCT, nine patients are alive and well, resulting in a disease-free and overall survival rate of 56.3% +/- 12.4%. The median overall survival has not yet been achieved. None of the patients who had surgery relapsed or died after therapy. All relapses occurred within the first 12 months after PBPCT. Patients in stages I to IIIA (10 patients) had a 70% +/- 14% overall survival rate at 4 years, while patients in stage IIIB (six patients) had a 33% +/- 19% survival rate at 4 years, with a median survival of 17 months posttransplant. These data demonstrate that a multimodality treatment including early high-dose chemotherapy with PBPCT may lead to a prolonged disease-free survival in the majority of patients. A randomized phase III study has now been initiated to prospectively investigate the role of high-dose chemotherapy, surgery, and chest irradiation in the multidisciplinary approach to limited-disease small cell lung cancer.

Adult↗
PubMed1997

A phase-I clinical study of autologous tumor cells plus interleukin-2-gene-transfected allogeneic fibroblasts as a vaccine in patients with cancer.

Tumor cells transfected to express immunostimulatory cytokines, or admixed with similarly modified bystander cells, are able to induce immune responses against unmodified tumor cells in animal models. For treatment of human patients, a vaccine composed of autologous tumor cells and IL-2-secreting allogeneic fibroblasts was developed. Autologous tumor cells were isolated from biopsy specimens. A clone (KMST 6.14) of an immortalized human fibroblast line that stably secreted 5290 IU IL-2 per 10(6) cells and per 24 hr was obtained by cationic lipofection with an expression construct for human IL-2 and Neo(r). Fifteen patients with refractory malignant tumors received 3-4 injections of irradiated KMST6.14 and autologous tumor cells in a phase-I clinical trial. Increasing transient inflammatory responses without systemic toxicity developed at vaccination sites and after injections with irradiated tumor cells only (p < 0.05). These sites contained a dense infiltrate of CD3+ T cells with numbers of CD4+ helper cells exceeding those of CD8+ cytotoxic T cells (CTL). CD8+ T-cell lines isolated from vaccination sites of 2 malignant melanoma patients but not of renal-cell carcinoma patients exhibited a dominant lytic activity against autologous tumor cells in vitro. CD8+ T-cell clones established from the vaccination site of 1 of 2 renal-cell carcinoma patients preferentially lysed autologous and partially matched allogeneic renal-cell carcinoma cells. In conclusion, a vaccine composed of IL-2 gene-transfected allogeneic fibroblasts and autologous tumor cells is able to enhance specific anti-tumor T-cell responses in vivo without major side-effects. Malignant melanoma and renal-cell carcinoma appear to be promising entities for testing of similar approaches in future therapeutic trials.

Adult↗
PubMed1997

Infiltration of lung carcinomas with macrophages of the 27E10-positive phenotype.

In order to gain insight into the role of macrophages in human lung carcinomas, we investigated material from 35 lung carcinomas and 5 healthy lungs with 4 different antibodies (CD68, MRP8, MRP14, 27E10) recognizing different macrophage subtypes. Infiltration with CD68-positive macrophages was highest and comparable in healthy lungs and lung carcinomas. Compared to healthy lungs, the infiltration of MRP8- and MRP14-positive macrophages was reduced in lung carcinomas while the number of 27E10-positive cells was enhanced. No difference in the infiltration of macrophages was observed between the different histological subtypes of carcinomas such as squamous carcinoma, small lung carcinoma, adenocarcinoma and bronchio-alveolar carcinoma. Furthermore, we present a highly suitable technique for the isolation and enrichment of macrophages from human lung carcinomas resulting in a 5-10 fold enrichment and a yield of e.g. 2-3 x 10(6) 27E10-positive macrophages/g tumor biopsy. Together with the recent findings that 27E10-positive macrophages are prevalent in early acute inflammation and release cytotoxic mediators and to inhibit tumor cell proliferation our findings suggest that 27E10-positive macrophages may play a role in antitumor cytotoxicity in human lung carcinomas.

Antibodies, Neoplasm↗
PubMed1997

Experimental gluing of the bronchial stump after pneumonectomy in rats.

OBJECTIVE: The objective of this experimental study was to evaluate the usefulness of gelatin-resorcinol-dialdehyde adhesive in sutureless closure of bronchial stumps. METHODS: In 40 male Wistar rats bronchial stumps after left-sided pneumonectomy were closed by gluing with gelatin-resorcinol-dialdehyde adhesive. For macroscopic and microscopic examination four animals were sacrificed on postoperative days 2, 7 and 14 each, 14 animals on postoperative days 28 and 120 each. RESULTS: On macroscopic examination the gelatin-resorcinol-dialdehyde adhesive proved in all cases effective in tight bronchial stump closure. The adhesive did not cause local infection or necrosis of the bronchial stump nor other intrathoracic inflammatory complications. All animals survived and made an uncomplicated postoperative recovery. Microscopic examination revealed that the gelatin-resorcinol-dialdehyde adhesive initially evoked an acute inflammatory response with polymorphonuclear neutrophils predominating. After an intermediate stage characterized by a granulomatous reaction and resorption of the adhesive by multinucleated giant cells, 120 days postoperatively the bronchial stumps at the sites of previous gluing showed a regular fibrous scar tissue without inflammatory cells. CONCLUSION: The gelatin-resorcinol-dialdehyde adhesive showed effective in closing bronchial stumps after pneumonectomy in rats. The clinical extrapolation of this effect to thoracic surgical patients is uncertain at this time.

Animals↗
PubMed1997

Results after surgery in undifferentiated large cell carcinoma of the lung: the role of neuroendocrine expression.

OBJECTIVE: The objective of this study was to define the incidence of light microscopically undifferentiated large cell carcinomas, to analyze tumor stages, types of resections necessary and postsurgical survival. Additionally we tried to evaluate whether or not neuroendocrine expression influences the biological behavior of these tumors. METHODS: Light microscopic specimens of 105 patients having undergone surgery for undifferentiated large cell carcinoma were reviewed following the 1981 WHO criteria. Fifty eight cases were excluded because elements of adeno- or squamous cell carcinoma, neuroendocrine or combined patterns of histological differentiation were observed. The remaining 47 cases of pure undifferentiated large cell carcinoma were evaluated immunohistochemically for neuroendocrine differentiation using a combination of the markers neuron specific enolase, synaptophysin and chromogranin A. The hospital charts of the patients were analyzed retrospectively recording tumor stage, operative procedure, postoperative complications, postoperative adjuvant treatment procedures, actual tumor state and survival time. RESULTS: Thirteen patients (27.7%) had postsurgical tumor stage I, 5 (10.6%) stage II, 15 (31.9%) stage IIIA, 9 (19.1%) stage IIIB, and 5 (10.6%) stage IV. In 46 of 47 patients resections of lung parenchyma were performed (wedge resection n = 5, segmental resection n = 1, lobectomy n = 27, bilobectomy n = 3, pneumonectomy n = 10), in 6 patients combined with broncho- and/or angioplastic procedures. At the time of chart review 20 (42.5%) patients were still alive. The cause of death in the remaining patients was recurrent lung cancer in the majority of cases (24 or 92.30%). The overall mean survival of the 46 patients undergoing parenchymal resections was 19 months, the 3-year survival rate 31.7%. The immunohistochemical examination demonstrated expression of neuron specific enolase in 15 cases. Synaptophysin and chromogranin A were not detected in any case. For these 15 patients the mean survival was 25.6 months (+/- 4.3) and the 1-year survival rate 67% (confidence interval 43-91%) compared to 13.8 (+/- 2.1) months and 33.5% (confidence interval 15.3-51.7%) in the remainder. The difference was not significant (P = 0.06). CONCLUSIONS: The light microscopic diagnosis of undifferentiated large cell carcinoma revealed to be subject to considerable interobserver variability. Undifferentiated large cell carcinoma takes a more unfavorable clinical course than other non-small cell carcinomas. Despite lack of statistical significance, expression of neuron specific enolase appeared to be associated with less aggressive biological behavior of the respective neoplasms. Immunohistochemical evaluation of undifferentiated large cell carcinomas using a combination of neuron specific enolase, chromogranin A, and synaptophysin did not provide more therapeutically relevant information than that obtained by light microscopic assessment.

Biomarkers, Tumor↗
PubMed1997

Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 107 consecutive patients with limited- and extensive-stage non-small-cell lung cancer.

BACKGROUND: We conducted a phase I/II trial to assess the feasibility and activity of combination chemotherapy with etoposide, ifosfamide, cisplatin, and epirubicin in limited-stage (LS, stage I-IIIB) and extensive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). End-points were treatment-related morbidity and mortality, response rate, duration of response, and survival. PATIENTS AND METHODS: Chemotherapy followed by granulocyte colony-stimulating factor was given at a dose of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2), and epirubicin (50 mg/m2) (VIP-E) to 107 patients with NSCLC. Twenty-five patients with qualifying responses proceeded to high-dose chemotherapy with autologous peripheral blood stem cell transplantation after etoposide (1500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. RESULTS OF CONVENTIONAL-DOSE VIP-E: 35 of 102 (34%) evaluable patients responded (2 CR's, 33 PR's), 33/102 patients (33%) showed no change (NC); the remainder of patients progressed with therapy (PD). Objective response rate was 68% (4% CR, 64% PR) in LS-NSCLC and 23% (1.4% CR, 21.4% PR) in ES-NSCLC. Median duration of survival was 13 months in LS-NSCLC and 5.5 months in ES-NSCLC. Two-year survival was 26% in LS and 2% in ES-NSCLC. RESULTS OF HIGH-DOSE VIC-E: 23 of 24 evaluable patients improved or maintained prior responses (92%), I patient showed NC. Treatment mortality was 4%. Median duration of survival was 17 months in LS-NSCLC and 10 months in ES-NSCLC. Two-year survival was 30% in LS and 8% in ES-NSCLC. CONCLUSION: Response-rates and survival after conventional-dose VIP-E chemotherapy are comparable to other published trials of combination chemotherapy in NSCLC. Toxicity and mortality is acceptable in limited stage, but unacceptably high in extensive stage NSCLC. Although better response-rates were achieved in the high-dose arm, they did not translate into improved survival. Most stage IV NSCLC-patients will neither benefit from VIP-E conventional dose, nor from VIC-E high dose chemotherapy. Whether selected LS-patients with partial or complete responses to VIP-E induction chemotherapy could benefit from dose intensification in an adjuvant or neo-adjuvant setting remains to be determined.

Adult↗
PubMed1997

Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited- and extensive-disease small-cell lung cancer.

BACKGROUND: We conducted a phase I/II trial to assess the feasibility and activity of VIP-E chemotherapy in small-cell lung cancer. End-points were treatment-related morbidity and mortality, response to treatment. duration of response, and survival. PATIENTS AND METHODS: Two cycles of combination chemotherapy followed by granulocyte colony-stimulating factor (G-CSF) were given at a dose of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2), and epirubicin (50 mg/m2) to 100 consecutive patients with SCLC. Thirty patients (19 with LD, and 11 with ED SCLC) proceeded to VIC-E high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) at a cumulative dose of etoposide 1500 mg/m2, ifosfamide 12,000 mg/m2, carboplatin 750 mg/m2 and epirubicin 150 mg/m2 (VIC-E). Surgical resection of primary tumor was attempted at the earliest feasible point. Thoracic irradiation was given after completion of chemotherapy. RESULTS of conventional-dose VIP-E: 97 patients were evaluable for response. Objective response rate was 81% in LD-SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED-SCLC (18% CR, 58% PR). Treatment mortality was 2%. Median survival was 19 months in LD-SCLC and 6 months in ED-SCLC. Two-year survival was 36% in LD and 0% in ED SCLC. RESULTS OF HIGH-DOSE VIC-E: All 30 patients improved on or maintained prior responses. Four patients (13%) died of treatment-related complications. Median survival was 26 months in LD-SCLC and 8 months in ED-SCLC. Two-year survival was 53% in LD and 9% in ED SCLC. CONCLUSION: VIP-E chemotherapy is an effective induction therapy for SCLC. Compared with traditional protocols such as ACO or carboplatin/etoposide, response rates are slightly improved, while survival is not different. In the LD SCLC subgroup, high-dose chemotherapy improved response rates and survival, especially for patients in surgical CR prior to high-dose therapy. In ED SCLC, however, higher response-rates did not translate into improved survival. Selected LD-SCLC patients with good partial or complete remissions after prior therapy may benefit from HDC and PBSCT.

Adult↗
PubMed1997

Experimental gluing of lung parenchyma in rats.

Gelatin-resorcinol-dialdehyde adhesive has been developed from a gelatin-resorcinol-formaldehyde adhesive by replacing the formaldehyde with two less histotoxic dialdehydes, ethandial and pentandial. The aim of the present study was to evaluate the usefulness of this modified composition in gluing defects in lung parenchyma. In 40 male Wistar rats a standardized lung incision 1.0 cm in length and 0.8 cm in depth were closed by application of gelatin-resorcinol-dialdehyde adhesive. For macroscopic and microscopic examination 4 animals were sacrificed on each of postoperative days 2, 7, and 14 and 14 animals on each of postoperative days 28 and 120. Macroscopic examination revealed a tight closure of the parenchymal defects in all postoperative stages. Initially by an adhesive layer and later on by granulation tissue and scar tissue respectively. On microscopic examination an inflammatory tissue response with polymorphonuclear neutrophils and macrophages predominating was found 2 days postoperatively. After 7 days multinucleated giant cells appeared. On postoperative day 14 the tissue response presented a distinct granulomatous character with multinucleated giant cells persisting. After 28 days remnants of adhesive surrounded by granulation tissue were detectable. On postoperative day 120 the adhesive had been completely resorbed and the parenchymal defect was replaced by fibrous scar tissue. The gelatin-resorcinol-adhesive proved effective in tight closure of lung parenchyma in rats. The adhesive is resorbed completely and does not interfere with parenchymal healing.

Absorption↗
PubMed1997

Long-term survival after repetitive surgery for malignant hemangiopericytoma of the lung with subsequent systemic metastases: case report and review of the literature.

Malignant hemangiopericytoma represent less than 1% of all vascular and about 5% of all sarcomatous tumors. We are reporting the uncommon clinical case of primary pulmonary localization, of which approximately 100 cases have been published in the literature. A 54-year-old male underwent left upper lobectomy seven years ago for a tumor which proved to be a malignant hemangiopericytoma. Six months later a metastasis in the abdominal wall in the epigastrium appeared and was completely excised without further treatment. During a follow-up of 16 months another metastasis developed in the mesenterium causing ileus and leading to laparotomy with resection of 120 cm small bowel. After this procedure followed by two cycles of chemotherapy the patient remained free of disease. Details of the clinical course and a review of the literature are presented.

Abdominal Neoplasms↗
PubMed1997

Processing of tumor tissues for vaccination with autologous tumor cells.

Vaccination with gene-transfected tumor cells has recently been proposed as a new strategy in the immunotherapy of cancer. Since autologous tumor cells provide an optimal antigen profile, the possibility of generating single cell suspensions from renal cell carcinoma (RCC), malignant melanoma (MM), colon carcinoma (CC), and non-small-cell lung cancer (NSCLC) biopsies was investigated. One hundred and seventy-four tumor biopsies were processed by mechanic and enzymatic dissociation, yielding 1-2 x 10(6) cells/g tumor (median), irrespective of tumor type. Primary tumor cell cultures (PTCC) of > or = 10(7) cells were established from 29 of 86 (34%) RCC, 14 of 38 (37%) MM, 11 of 23 (48%) NSCLC and 4 of 27 (15%) CC specimens. The amount of non-tumor cells, as assessed by morphology and immunocytology, was generally low (< 30%) in RCC (35 of 41) and MM (11 of 17), while it exceeded 60% in 8 of 11 PTCC from NSCLC and 3 of 11 CC. A high tumor cell yield was obtained in biopsies with a high degree of vascularization and in the virtual absence of necrosis. Thus, PTCC > or = 10(7) cells were obtained in 73% of MM with a high degree of vascularization and in 22% of MM with a low degree of vascularization (p < 0.007). Long-term tumor cell cultures exceeding 20 passages were established in 24 of 86 (18%) RCC, 7 of 38 (18%) MM and 3 of 27 (11%) CC, while successful implantation in nude mice was achieved in 8 of 20 RCC and 5 of 10 MM. Thus, under the conditions described, > or = 10(7) primary tumor cells of high purity could be generated from about one third of RCC and MM biopsies, while the success rate increased to > 50 and > 70%, respectively, in samples with a high degree of vascularization generated by an optimized biopsy technique excluding necrotic parts.

Animals↗
PubMed1996

Bilateral myoclonus of the trapezius muscles after distal lesion of an accessory nerve.

Observations of rhythmic or semirhythmic myoclonus due to a peripheral nerve lesion are exceptional. We report on a patient with thorax trauma with multiple bilateral hematomas of the paravertebral musculature. Eight years later he developed rhythmic myoclonus of both trapezius muscles and thoracic pain. Infiltration of a paramedially located scar at the level of D5-6 with a local anesthetic agent led to an intermittent relief of the myoclonus as did anesthetic blockade of the left accessory nerve. Surgical excision of the scar, which contained multiple dystrophic axons on histological examination, cured the patient's symptoms as illustrated in a videotape. This indicates that peripheral afferents contributed to the myoclonus. Ephaptic transmission, ectopic excitation, or misdirected neuronal sprouting secondary to the trauma are possible peripheral mechanisms responsible for the movement disorder. Successful blockade of the left accessory nerve with bilateral relief of the symptoms suggests a secondary, more centrally located mechanism, e.g., in the brain stem, probably driven by an altered afferent input. It is concluded that rhythmic or semirhythmic and focal myoclonus need a careful workup to look for a peripheral cause because such a condition would be accessible for surgical treatment.

Accessory Nerve↗
PubMed1996

[Surgical treatment of bronchial carcinoma in advanced age].

As live expectancy increases, the number of elderly patients 70 and more years of age are also increasingly represented in a thoracic surgical series. The preponderance of malignant disease in this group, particularly lung cancer, is common. Progress in anesthesia, intensive care and operative techniques in recent years has reduced the risk of morbidity and operative mortality in this age group. Operative and 30-day hospital mortality was 4.8% in our series.

Aged↗