Less intense conditioning with fludarabine, cyclophosphamide, idarubicin and etoposide (FCIE) followed by allogeneic unselected peripheral blood stem cell transplantation in elderly patients with leukemia.

The objective of this study was to assess toxicity and feasibility of achieving engraftment of allogeneic blood progenitor cells following nonmyeloablative conditioning according to the FCIE protocol (fludarabine 25 mg/m(2)/day, days -7 to -3; cyclophosphamide 200 mg/m(2)/day, days -7 to -3; idarubicin 12 mg/m(2)/day, days -7 to -5; etoposide 250 mg/m(2)/day, days -4 to -3) in elderly patients with leukemia. Eleven patients were included in the study: six patients with acute myeloid leukemia (AML) in complete remission (CR); three patients with refractory or relapsed AML; one patient with chronic myeloid leukemia; one patient with acute lymphoblastic leukemia. The median age of the patients was 62 years. All patients received blood progenitor cells from an HLA-identical sibling with 8.8 x 10(6) CD34(+) cells/kg (median; range 4.7 to 26.2 x 10(6)/kg) and 5.5 x 10(8) CD3(+)cells/kg (median; range 4.5 to 7.9 x 10(8)/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and three courses of methotrexate. The median duration of white blood cell counts <1 x 10(9)/l was 17 days and of platelet counts <50 x 10(9)/l 20 days. In two patients acute GVHD grade I occurred. Nine of 10 patients analyzed developed mixed chimerism. Of seven patients transplanted in CR, three remained in CR 19 to 31 months after transplantation. Three patients with refractory leukemia did not achieve CR, while the patient with relapsed AML achieved a 3rd CR. After a median follow-up time of 22 months, chronic GVHD was mild and limited. The data from this pilot study in elderly patients with leukemia show that the combination of primarily immunosuppressive (FC) and antileukemic (IE) drugs for nonmyeloablative conditioning has moderate nonhematological toxicity and allows engraftment of allogeneic blood progenitor cells.

The expression of the IGF family and GH receptor in the bovine mammary gland.

To study the involvement of the IGFs in mammary development and lactation of the cow, the temporal expressions of IGF-I and -II, its receptor type 1 (IGFR-1), IGF-binding proteins (IGFBPs)-1 to -6 and GH receptor (GHR) mRNA were examined. This was carried out for different stages of mammogenesis, lactogenesis, galactopoiesis and involution in the bovine mammary gland of 26 animals. Furthermore, IGF-I was localised by immunohistochemistry. The highest mRNA concentrations for IGF-I were detected in the mammary tissue of late pregnant heifers (days 255-272) and significantly lower expression was detected during lactogenesis and galactopoiesis. Immunohistochemistry of IGF-I revealed only a weak staining in the epithelium of the ducts during mammogenesis. The epithelium of the alveoli were negative during mammogenesis, lactogenesis and galactopoiesis but displayed distinct IGF-I activity during involution. In the stroma a distinct staining of the cytoplasm of adipocytes and of vascular smooth muscle cells was observed. A certain percentage of fibroblasts (usually 20-30%) were also immunopositive. In contrast, highest expression for IGFR-1 was detected during galactopoiesis and involution. The lowest mRNA concentration for IGFR-1 was found during pregnancy (days 194-213). In general, the expression of IGF-II was not regulated during mammogenesis and lactation, but decreased during involution. The mRNA for the six binding proteins was detected in the bovine mammary gland. The dominant binding proteins were IGFBP-3 and -5. The highest expression of IGFBP-3 was observed during mid-pregnancy and the lowest during late lactation, involution and in non-pregnant heifers. The mRNA for IGFBP-5 increased during late mammogenesis and lactogenesis followed by a decrease thereafter. In general, the mRNA concentrations for IGFBP-2, -4 and -6 were barely detectable during all stages. In contrast, the expression for IGFBP-1 was upregulated in the mammary gland of virgin heifers and increased around the onset of lactation. mRNA for GHR was found during all stages examined without outstanding fluctuations. In conclusion, locally produced IGF-I and -II may mediate mammogenesis. The high mammary IGFR-1 mRNA during lactation suggests a role for peripheral IGF-I in maintenance of lactation. The role of IGFBPs in the mammary gland needs further evaluation.

[Pulmonary varices (author's transl)]. / Intrapulmonale Varizen

In world literature up to now 41 cases of pulmonary varices have been described. Two own cases showed particulars in so far as one patient had an internal fistula between a varix in the base of the upper lobe of the lung and another varix in the apex of the lower lobe. Besides a varix the second patient had an AV-fistula in the right middle lobe. Already pre-operatively either case was diagnosed as vascular anomaly by angiography. By injecting the contrast medium into the vessels of the resection specimen a clear representation of the varices could be obtained.

Reoperation for bronchial carcinoma.

After a primary operation for bronchial carcinoma, 17 patients underwent reoperation for local recurrence or intrathoracic metastasis (nine squamous cell, five alveolar cell, and three adenocarcinomas). The average interval between the first and second operation was 23 months (range: six to 48 months). Twelve patients had a pneumonectomy after an initial ipsilateral lobectomy. Five patients underwent contralateral wedge excision after initial lobectomy or wedge excision. Three patients died within 30 days of the reoperation. Eight of the remaining 14 patients died subsequently, the time of survival averaging 18 months (range: three to 54 months). Six patients are still alive, two having survived their reoperation for more than five years. Reoperation for recurrent bronchial carcinoma is rarely performed, but it should be considered in all cases where patients survive operation for lung cancer if the primary operation was thought to be radical.

Criteria of functional operability in patients with bronchial carcinoma: preoperative assessment of risk and prediction of postoperative function.

In this prospective study of 433 patients undergoing surgery for bronchial carcinoma 3 main factors influencing the operative risk were identified: (1) extent of resection, (2) pulmonary function and (3) age. The 30-day mortality rate was 8.3% in the whole group which comprised a high percentage of patients over 70 years of age (27%) and with a disturbed pulmonary function (45%). The value of various functional criteria proposed in the extensive literature is assessed and compared with the results of the study in which the use of FEV1 and quantitative regional analysis by perfusion scanning and 'regions of interest' proved to be highly efficient, allowing, in addition, the prediction of postoperative lung function even in sleeve resections. A new formula for estimation of the additional loss of function in the early postoperative phase after lobectomies is proposed along with a flow sheet for routine preoperative evaluation of pulmonary function.

[Standardised antibiotic therapy in major lung surgery (author's transl)]. / Standardisierte antibiotische Therapie in der grossen Lungenchirurgie.

Sputum and bronchial biopsies and smears were obtained from 221 patients who had undergone partial pneumonectomy without preceding antibiotic therapy. The results of 343 sputum examinations and of 126 bacteriological examinations of biopsies and smears were evaluated. Pathogenic bacteria were demonstrated in about 50% of the sputa and in about 25% of the biopsies and swabs. Anaerobic micro-organisms were extremely rare. Treatment was with tetracycline. Before antibiotic therapy Haemophilus influenzae, staphylococci and E. coli predominated, afterwards there were practically only staphylococci and Esch. coli. The incidence of primary resistance to the usual antibiotics was high, especially in respect of gram-negative organisms. The difference in incidence between primary and secondary resistance was one of degree. The least effective agents were ampicillin and amoxicillin, the most active were the aminoglycosides. Erycin proved satisfactory in infections with grampositive organisms while the cephalosporins were active against both gram-positive and gram-negative bacteria. The development of resistance and the clinical picture suggest that "eradication" of the infection during the postoperative stage is not advisable as it causes the selection of more or less drug-resistant organisms. A more satisfactory approach is gradually to reduce the infection until the immediate postoperative stage is over. Macroscopic and microscopic examination of the sputum is important, as the choice of the appropriate antibiotic is determined by the result of gram-staining.

Bronchial carcinoma and long-term survival. Retrospective study of 433 patients who underwent resection.

The long-term follow-up of patients with bronchial carcinoma treated by surgery is presented. Of 471 patients who underwent thoracotomy, the tumour could not be resected in 38 (8%). Sixty-three (13.4%) died within the first four weeks; 125 (28.9%) survived more than five years. A high percentage developed either late metastases, late recurrences, or a second primary lung carcinoma. The results of surgical resection for bronchial carcinoma cannot be considered satisfactory, although resection remains the best treatment even in those patients with an apparently unfavourable prognosis. In spite of reservations regarding retrospective studies, conclusions can be drawn regarding diagnosis, therapy, and prognosis. Questions concerning histological type, size, and site of tumour, and tumour stage can be answered only after an adequate postoperative interval. Five years after operation the patient who has apparently been successfully treated may die from a second primary carcinoma.

[Chest trauma--a challenge to the general surgeon and chest surgeon for co-operation (author's transl)]. / Das Thoraxtrauma--eine Herausforderung zur Kooperation von Allgemeinchirurgie und Lungenchirurgie.

During 1968-1977 86 persons with chest trauma were treated at the Chest Clinic Heckeshorn. Until 1973 only a few cases of, mostly slight, chest injuries were admitted and treatment was mainly concerned with pneumothorax and haemothorax induced by fracture of ribs. Since 1974, however, cases of chest trauma have markedly increased in both number and seriousness of the injury. During the past years 50 patients with chest injuries were treated. They included 6 cases of stab wounds, 4 cases of bullet wounds and one case each of damage to the trachea and bronchial rupture respectively. Thoracotomy was performed in 11 of the 50 patients, in 3 cases to stabilize the chest wall. Willingness to cooperate on the part of the general surgeon has made it possible for the surgically trained lung specialist to participate in chest traumatology.

[Results of continuous suction drainage in the treatment of pleural empyema (author's transl)]. / Ergebnisse der Dauersaugdrainagebehandlung beim Pleuraempyem.

201 adults with non-specific pleural empyema (58 women, 143 men) had suction drainage. Most of the patients were aged 61-70 years. In the 47 patients who had not had antibiotic therapy before admission the main causal micro-organisms were staphylococci, pneumococci and streptococci; in the 149, who had had antibiotic therapy outside, micro-organisms such as Pseudomonas, Esch. coli and Proteus predominated. Suction drainage had to be kept up for a remarkably long time: for 4-8 weeks in 36% of the cases and for more than 8 weeks in 8%. 31 patients died, but only 17 of them as a direct result of the pleural empyema. They had all been "high risk" cases on account of age (average 67.7 years), type of bacteria (59%), serious primary or complicating disease (59%), duration of the pleural empyema (76%). Suction drainage succeeded in 140 patients in clearing the infection; but marked adhesions were demonstrable in 27% of the patients when they were discharged from hospital.

Insulin-like and fibroblast growth factors and their receptors are differentially expressed in the oviducts of the common marmoset monkey (Callithrix jacchus) during the ovulatory cycle.

It is suggested that growth factors support the process of maturation and differentiation in the mammalian oviduct. Fibroblast growth factors (FGF) and insulin-like growth factors (IGF) are possible influences on these processes. The present study describes for the first time the expression of FGF-1 and -2 and their receptors as well as IGF-1 and -2 and the corresponding IGF receptor type 1 in the oviduct of the New World monkey Callithrix jacchus. Because of the limited RNA yields from oviducts, reverse transcription-polymerase chain reaction (RT-PCR) was performed to estimate expression levels. Expression patterns were found to be similar for all examined growth factors and receptors: the highest mRNA contents were obtained at the late proliferative and early to midsecretory phases, compared with lower levels during the early proliferative phase. Elevated amounts of these RNAs were correlated with high serum estradiol but not with progesterone concentrations. Each PCR product showed a high degree of homology (> 92%) to the known human sequences. Immunohistochemical analysis indicated greater specific staining for FGF-1 and -2 and IGF-1 before ovulation on the luminal epithelial surface of marmoset oviducts in comparison to the other cycle phases. Differences in staining intensity were not observed between the ampulla and isthmus. In summary, the marmoset oviduct expresses all components of functional FGF and IGF systems, thus suggesting auto-/paracrine effects of these growth factors within the primate oviduct, possibly under the control of estrogenic hormones.

Expression pattern of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) system members in bovine corpus luteum endothelial cells during treatment with FGF-2, VEGF or oestradiol.

The development of the corpus luteum (CL) is accompanied by very active angiogenesis. We hypothesize that during this process endothelial cells (EC) are under the control of several angiogenic factors and steroids. The aim of this study was to examine the expression of the angiogenic growth factor systems - fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) - in EC derived from the bovine CL. Endothelial cells were cultured in serum-free medium and treated for 24 h with different concentrations of oestradiol (range from 10(-13) to 10(-5) mol/l), VEGF or FGF-2 (1, 10 and 100 ng/ml, respectively) and compared with untreated controls. Cells were harvested, total RNA extracted and subjected to semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Treatment with oestradiol or FGF-2 stimulated the expression of FGF-2, but VEGF treatment showed no effect on the FGF-2 expression. FGF-2 or VEGF treatment resulted in an up-regulation of the FGF receptor (FGFR) mRNA. However, no FGF-1 expression was detected in EC. For the VEGF system, treatment with FGF-2, VEGF or oestradiol did not affect VEGF expression. However, the presence of FGF-2 in the medium up-regulated the expression of both VEGF receptors (VEGFR-1 and VEGFR-2), whereas oestradiol or VEGF treatment showed no effect on the expression of these receptors. Our results reveal that functional angiogenic growth factor systems were expressed in vitro in bovine EC derived from the CL. This suggests that the angiogenic FGF and VEGF system members were regulated by FGF or VEGF, but not by oestradiol-17beta.