Stored perfume dynamics and consequences for signal development in male orchid bees.

Male orchid bees (Euglossini) collect volatiles from their environment to concoct species-specific "perfumes", which are later emitted at mating sites. Intensity, complexity or composition of perfumes may encode age (survival) of a male, but how the individual perfume develops over time needs to be clarified. We investigated chemical changes during storage in leg pockets. We injected a mixture of eight perfume compounds into pockets of Euglossa imperialis and only the two most volatile compounds decreased over 12 days. Using a different approach we found significant shifts in quantities of naturally occurring perfume compounds of Euglossa championi over 10 days, with the strongest decreases (up to 70% peak area) in highly volatile minor compounds, e.g. monoterpenes, and noteworthy increases (up to 40%) in some sesquiterpenoids. Corresponding shifts were observed in legs of dried bees, suggesting that no metabolic activity is required for the observed changes to occur. Our results confirm that male orchid bees are generally good at preserving collected perfumes. However, subtle shifts towards heavier compounds in blends may occur over the lifetime of individual bees, e.g. due to evaporation or in-pocket chemical reaction, with old males acquiring a more pronounced base note in their seasoned perfumes.

Gemcitabine, vinorelbine and cisplatin combination chemotherapy in advanced non-small cell lung cancer: a phase II trial.

The purpose of this phase II trial was to investigate the efficacy and safety of a combination chemotherapy with gemcitabine, vinorelbine and cisplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Patients with NSCLC stage IIIB or IV disease received 1000 mg/m(2) gemcitabine and 25 mg/m(2) vinorelbine on days 1 and 8 and 75 mg/m(2) cisplatin on day 2, every 3 weeks. From December 1998 to May 1999, 31 patients (21 stage IV and 10 stage IIIB disease), with a median age of 59 years (range 40-72 years) were enrolled. The overall intent-to-treat response rate was 45% (95% confidence interval (CI): 27-64%) with 2 complete responders (CR) and 12 partial responders (PR), 7 patients had stable disease and 10 progressed. Median survival was 12.8 months (95% CI: 6.5-12.8+ months), median time to progression was 5.1 months (95% CI: 3.5-7.7 months), and the 1-year survival rate was 52.9% (95% CI: 36.7-76.2%). Patients with stage IIIB disease had a significantly longer overall survival than patients with stage IV disease (P=0.05). Transient World Health Organization (WHO) grade IV leucopenia, anaemia and thrombocytopenia occurred in 3 (10%), 2 (6%) and 3 (10%) patients, respectively. The predominant non-haematological toxicities were alopecia and nausea/vomiting. 15 patients (48%) had WHO grade II and III alopecia and 14 patients (45%) nausea/vomiting. The combination of gemcitabine, vinorelbine and cisplatin has demonstrated major antitumour efficacy in advanced NSCLC with a manageable toxicity profile.

Lymphatic mapping of sentinel nodes in early vulvar cancer.

OBJECTIVE: The aim of the study was to determine the diagnostic accuracy and feasibility of sentinel lymph node (SLN) detection using a gamma probe in patients suffering from vulvar cancer. METHODS: From May 1998 to November 2000, 26 patients with early vulvar cancer, planned for local wide excision or vulvectomy including groin dissection, were eligible for the study. Two to 3 h before the planned procedure we injected technetium(99) m-labeled microcolloid intradermally at four locations around the tumor. Dynamic and static images were recorded using a gamma camera. SLN locations were marked on the overlying skin. In the operating theater SLNs were identified at the beginning of the procedure using a handheld gamma-detection probe. After resection of suspected SLNs a standard unilateral or bilateral groin dissection was performed, subsequently followed by local wide excision or, if indicated, radical vulvectomy. Sentinel node detection using technetium(99) m-labeled microcolloid was compared with final histopathological and immunohistochemical results. RESULTS: Scintigraphy showed focal uptake in all 26 patients. Intraoperatively we detected all sentinel nodes by handheld gamma probe. In 20 patients, one sentinel node was identified unilaterally, while in 6 patients two or more nodes were identified bilaterally. Histologically positive SLNs were found in 9 patients. In our preliminary series we did not find any false-negative SLN. CONCLUSION: Identification of sentinel nodes in vulvar cancer is feasible with preoperatively administered technetium(99)m-labeled microcolloid. We confirm the results of previous studies and improve the evidence that the SLN procedure could be implemented in future therapy concepts.

Sentinel node procedure in Ib cervical cancer: a preliminary series.

The aim of this study was to determine the diagnostic accuracy and feasibility of sentinel lymph node (SLN) detection using a gamma probe in patients with Figo IB cervical cancer. Between January 1999 and September 2000, 14 patients with cervical cancer, planned for radical hysterectomy were eligible for the study. The day before radical hysterectomy we injected technetium(99)m-labelled nanocolloid in each quadrant of the cervix. Dynamic and static images were recorded using a gamma camera. SLNs were identified intraoperatively using a handheld gamma-detection probe. After resection of SLNs a standard radical hysterectomy with pelvic lymph node dissection was performed. Patients and tumour characteristics were compared with sentinel node detection and with final histopathological and immunohistochemical results. Scintigraphy showed focal uptake in 13 of the 14 patients. Intraoperatively we detected 26 sentinel nodes by gamma probe. In 8 of 13 patients, one or more sentinel nodes were identified unilaterally, in 5 women bilaterally. Histologically positive SLNs were found in only 1 patient. We did not find any false-negative SLN in our series. In conclusion identification of sentinel nodes in cervical cancer is feasible with preoperatively administered technetium(99)m-labelled nanocolloid. A larger series will be required to establish sentinel node detection in cervical cancer for further therapy concepts and planning.

Gemcitabine and vinorelbine as first-line chemotherapy for advanced non-small cell lung cancer: a phase II trial.

The purpose of this phase II study was to investigate the efficacy and safety of gemcitabine plus vinorelbine as first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Eligibility criteria included cytologically or histologically confirmed NSCLC (stage IIIB or IV), no previous chemotherapy, and bidimensionally measurable disease. Patients received 1000 mg/m(2) gemcitabine and 30 mg/m(2) vinorelbine on days 1, 8 and 15 every 4 weeks up to eight courses. From December 1997 to November 1998, 70 patients (59 stage IV and 11 stage IIIB disease), with a median age of 59 years (range 38-74 years) were enrolled. The intent-to-treat response rate was 41% (95% confidence interval (CI) 30-54%) with 1 complete responder (CR) and 28 partial responders (PRs), 15 patients had stable disease (SD) and 26 progressed (PD). Median survival was 8.3 months (95% CI 6.0-9.9 months), median progression-free survival (PFS) was 4.8 months (95% CI 3.9-5.5 months), and 1-year survival rate was 33.5% (95% CI 24.0-46.8%). Patients received a total of 229 cycles. Haematological and non-haematological toxicities were moderate. Transient World Health Organization (WHO)-grade IV leucopenia and thrombocytopenia occurred in 13 (6%) and two (1%) cycles, respectively. The predominant non-haematological toxicity was local reactions of the veins in 19 (27%) patients (WHO-grade II and III). Neurotoxicity was infrequent, non-cumulative, and reversible. The combination of gemcitabine and vinorelbine has demonstrated activity in metastatic NSCLC, with response and survival rates similar to those of cisplatin-based regimens and a more favourable toxicity profile that is well tolerated in an outpatient setting.

A clinical trial of edrecolomab, interleukin-2 and GM-CSF in patients with advanced colorectal cancer.

Immunological effector mechanisms of monoclonal antibodies such as antibody-dependent cytotoxicity can be augmented by the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2). Therefore twelve patients with metastatic colorectal cancer were treated with 300 microg GM-CSF and 6 million units IL-2 subcutaneously daily from day 1 to 10 followed by a three week rest period. Of the edrecolomab 400 mg was given on day 3 of the first cycle. The dose was reduced to 150 mg on subsequent cycles. A maximum of four cycles was administered. Toxicity was manageable on an outpatient basis. No partial or complete responses were observed in these 12 patients. Median time to treatment failure was 67 days and median survival 287 days. Immunological parameters were monitored throughout the study.

Hand-foot syndrome associated with short infusions of combination chemotherapy with gemcitabine and vinorelbine.

The hand-foot syndrome (palmar-plantar erythrodysesthesia) is a side-effect which is associated with several cytotoxic agents (e.g. 5-fluorouracil, UFT, capecitabine, cytarabine, doxorubicin, liposomal-encapsulated doxorubicin). An association with a prolonged infusion of high doses of vinorelbine has also been described. To date a hand-foot syndrome after gemcitabine or short infusions of vinorelbine has not been reported before. The patient described here had a non-small-cell lung cancer stage IIIB disease and developed a hand-foot syndrome after short infusions of standard-dose chemotherapy of a combination with gemcitabine and vinorelbine.

In vitro differentiation of endothelial cells from AC133-positive progenitor cells.

Recent findings support the hypothesis that the CD34(+)-cell population in bone marrow and peripheral blood contains hematopoietic and endothelial progenitor and stem cells. In this study, we report that human AC133(+) cells from granulocyte colony-stimulating factor-mobilized peripheral blood have the capacity to differentiate into endothelial cells (ECs). When cultured in the presence of vascular endothelial growth factor (VEGF) and the novel cytokine stem cell growth factor (SCGF), AC133(+) progenitors generate both adherent and proliferating nonadherent cells. Phenotypic analysis of the cells within the adherent population reveals that the majority display endothelial features, including the expression of KDR, Tie-2, Ulex europaeus agglutinin-1, and von Willebrand factor. Electron microscopic studies of these cells show structures compatible with Weibel-Palade bodies that are found exclusively in vascular endothelium. AC133-derived nonadherent cells give rise to both hematopoietic and endothelial colonies in semisolid medium. On transfer to fresh liquid culture with VEGF and SCGF, nonadherent cells again produce an adherent and a nonadherent population. In mice with severe combined immunodeficiency, AC133-derived cells form new blood vessels in vivo when injected subcutaneously together with A549 lung cancer cells. These data indicate that the AC133(+)-cell population consists of progenitor and stem cells not only with hematopoietic potential but also with the capacity to differentiate into ECs. Whether these hematopoietic and endothelial progenitors develop from a common precursor, the hemangioblast will be studied at the single-cell level.

Somatostatin receptor scintigraphy in patients with pituitary adenoma.

Presence of high-affinity somatostatin (SST) receptors in most endocrine tumor cells allow in vivo scintigraphic visualization of these neoplasms after intravenous administration of a radionuclide-labeled somatostatin analog. 111In-octreotide is at present the most often used substance for imaging of the SST receptor expression in vivo. The aim of this study is to investigate the correlation between presence of in vivo scintigraphically detectable SST receptors in pituitary tumors and clinical parameters such as patients' age, tumor size, hormonal hypersecretion, and response to octreotide therapy. Forty-two-consecutive patients were enrolled in this trial. Twenty-five of them had nonsecreting pituitary tumors, 11 were acromegalic, and 6 had macro- or microprolactinoma. Scintigraphic images of the head were obtained at 10 min and 24 hours after injection of the radionuclide. In 23 patients, no specific binding of 111In-octreotide was found. Five patients showed a weak positive, 5 had a positive, and 9 a strong positive signal in the region of interest. Uptake of octreotide was significantly correlated with tumor size and age (p < 0.01). Small-size pituitary adenomas were most likely to be scintigraphically receptor-negative, while large suprasellar tumors tended to exhibit a rather strong receptor positivity. Statistical analysis of the data could not confirm the hypothesized correlation between endocrine activity of the pituitary tumors and the scintigraphically proven SST receptor expression in vivo. A positive Octreoscan was not predictive for the result of octreotide therapy.

[Open foramen ovale in patients with arterial vascular occlusions of the retina and optic nerve]. / Offenes Foramen ovale bei Patienten mit arteriellen Gefässverschlüssen der Netzhaut und des Sehnervs.

BACKGROUND: We examined the frequency and significance of persistent foramen ovale (PFO) in patients with ocular circulatory disturbance. PATIENTS AND METHODS: Forty patients with acute arterial occlusions of the posterior bulb segment were investigated by means of transthoracic and transesophageal echocardiography (TEE). The parallel presence of cerebral ischemia was clarified on the basis of existing CCT findings and by additional HMPAO-SPECT investigation. RESULTS: PFO was identified in nine of the patients investigated. The probability of paradoxical embolism arises from further findings: eight of those with PFO (89%) showed echocardiographic signs of right heart strain, indicating previous pulmonary embolism, compared with only three of those without PFO (10%). Five of those with PFO showed a potential source of embolism, two of them with phlebothromboses in their clinical history and three with additional atrial septal aneurysm. Cardiovascular risk factors were prevalent in the group without PFO. Both groups had a mean age of approximately 60 years. Signs of cerebral ischemia were present in the SPECT or CT findings for four of the patients with PFO and nine of those without. CONCLUSIONS: From our findings, it appears highly probable that ocular arterial occlusion is caused by paradoxical embolism. PFO should be taken into account in establishing a diagnosis, including diagnosis in elderly patients.

Development of the low-T3-syndrome and prognosis assessment in patients with liver cirrhosis.

The aim of our study is to prove whether the development of the low-T3-syndrome in patients with liver cirrhosis is associated with their prognosis. For this purpose we determined the peripheral thyroid hormone levels in 28 patients with liver cirrhosis. For prognosis assessment we calculated the Prognostic Index (PI) on the basis of Cox's regression model as recently described by us. Calculating this index we used 11 parameters: liver morphology, consciousness, spider naevi, PCV, thrombocytes, gamma-GT, cholesterol, albumin, Quick's value, IgA, and potassium. It is demonstrated that there is an inverse correlation between T3-serum levels and PI (p = 0.03). An association could not be detected neither between reverse T3 and PI nor between T3 and rT3. On the other hand basal TSH was also inversely associated with PI. Thus, the low T3-serum levels did not induce a rise of basal TSH in cirrhotics. Moreover, the mean serum-T3-concentration differed significantly from that of 6 decreased patients and from that of the surviving (p = 0.00076). It seems to be true that low T3-serum levels are a very sensitive parameter for prognosis prediction in patients with liver cirrhosis.

[Risk assessment of bronchial cancer surgery using quantitative lung perfusion scintigraphy]. / Risikoeinschätzung einer operativen Therapie des Bronchialkarzinoms mit Hilfe der quantitativen Lungenperfusionsszintigraphie.

28 patients with bronchogenic carcinoma were studied to predict lung function after thoracic resectional surgery, i.e. the functional operability, employing preoperative vital capacity (VC), forced expiratory volume (FEV1) and perfusion lung imaging. The perfusion scan was divided into 12 regions of interest which were semiquantitated to determine the relative distribution of perfusion as a fraction of the total perfusion. The planned reduction of lung parenchyma was expressed as percent of total perfusion, and the expected decrease in VC and FEV1, i.e. the predicted postoperative function of the lung, was calculated. The comparison of the predicted functional lung capacity with the re-estimated lung function (VC and FEF1) 6 months after surgery showed high correlation coefficients for both VC and FEV1. Semiquantitative perfusion scintigraphy of the lung helps to determine the extent of surgery possible in the individual therapy of lung cancer and is especially important in patients with a high operative risk.

[Standardization of methods and assessment of conventional and radionuclide clearance investigations: recommendations of the Renal Diagnostics Study Group of the Society of Nephrology, GDR]. / Vereinheitlichte Methodik und Beurteilung der konventionellen und nuklearmedizinischen Clearance-Untersuchungen: Empfehlungen der Arbeitsgruppe "Nierenfunktionsdiagnostik" in der Gesellschaft für Nephrologie der DDR.

Recommendations of the Study Group "Renal Function Diagnostics" of the Society of Nephrology to the performance of the steady state clearance using inulin or PAH and the slope clearance with radionuclides for estimation of effective renal plasma flow are presented. These investigations are indicated in the early recognition and follow-up of latent or residual disturbance of the renal function in the creatinine-blind area. Recommendations have been done on selection and dosage of test substances, timing of examination and evaluation of results.

[Nuclear medicine functional diagnosis of the myocardium using (123) I-heptadecanoic acid]. / Nuklearmedizinische Funktionsdiagnostik des Myokards unter Anwendung von 123I-Heptadekansäure.

On the basis of the results which we obtained having performed 25 examinations on 15 patients with angina pectoris syndrome, myocardial infarctions and condition after bypass operation the preparation 123I hepatadecanoic acid produced in the Central Institute for Nuclear Research Rossendorf is very well suited for the scintigraphic demonstration of the myocardium. Moreover it is possible to recognize selectively diagnostically interesting regions with different radioactivity intake, retention and elimination of the radiopharmacon pharmacon and with the help of quantitative parameters to characterize concerning the metabolic efficiency. We consider the 123I hepatadecanoic acid suitable for the clinical use in establishing the global and regional metabolic efficiency of the myocardium. It is very well to be used for the primary diagnostics and represents an evident diagnostic remedy for the assessment of the course of myocardial diseases and the success of therapy.

Modification of adenylate cyclase by photoaffinity analogs of forskolin.

Photoaffinity labeling analogs of the adenylate cyclase activator forskolin (PF) have been synthesized, purified and tested for their effect on preparations of membrane-bound, Lubrol solubilized and forskolin affinity-purified adenylate cyclase (AC). All analogs of forskolin significantly activated AC. However, in the presence of 0.1 to 0.3 microM forskolin, the less active forskolin photoaffinity probes at 100 microM caused inhibition. This inhibition was dose-dependent for PF, suggesting that PF may complete with F for the same binding site(s). After cross-linking [125I]PF-M (see Figure 1 for structure) to either membrane or Lubrol-solubilized AC preparations by photolysis, a radiolabeled 100-110 kDa protein band was observed after autoradiography following SDS-PAGE. F at 100 microM blocked the photoradiolabeling of this protein. Radioiodination of forskolin-affinity purified AC showed several protein bands on autoradiogram, however, only one band (Mr = 100-110 kDa) was specifically labeled by [125I]PF-M following photolysis. The photoaffinity-labeled protein of 100-110 kDa of AC preparation of rat adipocyte may be the catalytic unit of adenylate cyclase of rat adipocyte itself as supported by the facts that [a] no other AC-regulatory proteins are known to be of this size, [b] the catalytic unit of bovine brain enzyme is in the same range and [c] this PF specifically stimulates AC activity when assayed alone, and weekly inhibits forskolin-activation of cyclase. These studies indicate that radiolabeled PF probes may be useful for photolabeling and detecting the catalytic unit of adenylate cyclase.

[Myocardial scintigraphy using omega-I-123 heptadecanoic acid (Rossendorf) in patients with coronary disease]. / Die Myokardszintigraphie mit Omega-123I-Heptadekansäure (Rossendorf) bei Patienten mit koronarer Herzkrankheit.

Scintigraphy using labelled myocardial metabolism precursors makes possible a noninvasive qualitative--and increasingly also quantitative--evaluation of global and regional myocardium, both normally and insufficiently perfused, with normal and disturbed metabolism. Among the labelled precursors, free fatty acids appear as most important, especially the omega-123I-heptadecanoic acid. The experience with the use of this myocardial metabolism precursor in 23 examinations of 11 patients is described.

Brevetoxin binding: molecular pharmacology versus immunoassay.

Brevetoxin PbTx-3 isolated from Florida's red tide dinoflagellate Ptychodiscus brevis has been produced recently in tritiated form by reductive tritiation of brevetoxin PbTx-2. Tritiated PbTx-3 has been used as a specific probe in competitive radioimmunoassays developed to detect brevetoxins in food sources, and this probe has also been utilized to characterize the brevetoxin binding component in rat brain synaptosomes. Brevetoxins PbTx-2 and PbTx-3, possessing the same structural backbone (type-1) as the tritiated probe, and PbTx-1 and PbTx-7, possessing a second structural backbone (type-2), have been compared quantitatively in their individual abilities to competitively displace tritiated PbTx-3 from its specific binding site in each assay. Type-1 toxins displaced labeled probe with ED50 values of 20-22 nM and 12-17 nM in radioimmunoassay and synaptosomes, respectively. Type-2 toxins displaced labeled probe with ED50 values of 92-93 nM and 3.5-4.1 nM in RIA and synaptosomes, respectively. Synaptosome assays reflect potency of each toxin examined, while radioimmunoassay reflects structural similarities to the immunizing toxin PbTx-3.

Brevetoxins, unique activators of voltage-sensitive sodium channels, bind to specific sites in rat brain synaptosomes.

The polyether lipid-soluble toxins isolated from the marine dinoflagellate Ptychodiscus brevis (formerly Gymnodinium breve) have been determined to bind to a unique site associated with rat brain synaptosomes. Using [3H]brevetoxin PbTx-3 as a specific probe, binding was determined at 4 degrees in rat brain synaptosomes using a rapid centrifugation technique. Rosenthal analysis yields a KD of 2.9 nM and a Bmax of 6.8 pmol of toxin/mg of protein. Labeled probe can be displaced by unlabeled PbTx-3, PbTx-2, or synthetic PbTx-3 (reduced PbTx-2) but not by a nontoxic, synthetic oxidized derivative of PbTx-2. Competition experiments using natural toxin probes specific for sites 1-4 of the voltage-dependent sodium channel have illustrated that PbTx-3 does not bind to any of the previously described sites associated with the channel. A fifth site is proposed. In addition, because of the varied nomenclature associated with the brevetoxins, a new classification system is proposed.