Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients. PATIENTS AND METHODS: ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line ≥12 weeks. RESULTS: Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC {hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36}. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade ≥3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002). CONCLUSIONS: In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted.

[Non-Small Cell Lung Cancer - Development of Parallel Mechanisms of Resistance]. / Nicht kleinzelliges Lungenkarzinom ­ doppelte Resistenzentwicklung.

Acquired resistances to tyrosine kinase inhibitors in non-small cell lung cancer develop after 9 - 12 month. In 60 % of the cases these resistances arise because of a secondary EGFR-T790 M resistance mutation. This report is describing the case of a patient who developed parallel two different mechanisms of resistance: A T790 M resistance mutation and a transformation into a small cell neuroendocrine cancer. Under therapy with Osimertinib and chemotherapy with carboplatin and etoposide the tumor responsed partially.

[Subgroup Analysis of the Non-interventional REASON Study: PFS and OS According to Age, Smoking History, Gender, and Histology in NSCLC Patients Treated with Gefitinib or Chemotherapy]. / Subgruppenanalyse aus der nicht-interventionellen Beobachtungsstudie REASON: PFS und OS gemäß Alter, Raucherstatus, Geschlecht und histologischem Subtyp unter Verwendung von Gefitinib bzw. chemotherapeutischer Behandlung bei NSCLC-Patienten.

PURPOSE: Assessment of several clinical factors on progression-free (PFS) and overall survival (OS) in NSCLC patients (pts.) (stage IV) with mutated epidermal growth factor receptor (EGFRm+) treated with gefitinib (gef) or with chemotherapy (CT) under real-world conditions. METHODS: 285 EGFRm+ pts. of the non-interventional REASON study treated with gef (n = 206) or CT (n = 79) as first-line therapy or with gef (n = 213) or CT (n = 61) in any line throughout the course of therapy were analyzed according to age, gender, smoking history and histology. RESULTS: Compared with CT, patients treated with gef showed prolongation of PFS and OS in all subgroups. PFS was significantly increased in women and non-smokers. OS was significantly increased in women, non-smokers, (ex)-smokers, patients with adenocarcinoma and elderly patients when treated with gef compared to CT. Female gender turned out to be an independent positive predictive factor for OS in patients treated with gef (HRmale: 1.74, p = 0.0009). CONCLUSION: A clinical benefit of gef was shown for all analyzed clinical subgroups of EGFRm+ pts. This was confirmed for the female gender in a multivariate analysis.

[Exon-dependent Subgroup-analysis of the Non-interventional REASON-Study: PFS and OS in EGFR-mutated NSCLC Patients Treated with Gefitinib or Chemotherapy]. / Exonabhängige Subgruppenanalyse der nicht-interventionellen REASON-Studie: PFS und OS beim EGFR-mutierten NSCLC mit Behandlung von Gefitinib versus Chemotherapie.

PURPOSE: To analyze the influence of the localization of mutations in the epidermal growth factor receptor (EGFR) gene on progression-free (PFS) and overall survival (OS) in patients (pts) with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with gefitinib (gef) or chemotherapy (CT) under real world conditions within the REASON study. METHODS: Subgroups of pts with mutations in exon 19 (n = 141), 18/20 (n = 43), and 21 (n = 104) were analyzed for PFS and OS according to gef or CT treatment and compared using the log-rank test. RESULTS: Pts with mutations in exon 19 and 18/20 treated with gef as first line therapy showed increased PFS and OS compared to CT. This increase was statistically significant in pts with exon 19 mutation (11.3 vs. 6.5 months), but was not found in pts with exon 21 mutation (9.1 vs. 9.3 months). Also, OS was significantly increased in patients with mutation in exon 19 treated with gef ever over all treatment lines compared to CT (21.8 vs. 10.6 months), whereas this was not found in pts with mutation in exon 21 (14.1 vs. 13.9 months). CONCLUSION: Localization and nature of EGFR mutations influences gefitinib treatment outcomes under routine conditions and should therefore be analyzed in detail.

Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small-cell lung cancer (NSCLC) patients: results of an open-label, randomized, controlled phase II study (CERTO).

BACKGROUND: This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v. (CIL-once) or 2×/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary end point was progression-free survival (PFS; independent read); secondary end points included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200. RESULTS: There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P = 0.085]; for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P = 0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvß3 and αvß5 expression was neither a predictive nor a prognostic indicator. CONCLUSIONS: The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across end points suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment. CLINICAL TRIAL REGISTRATION ID NUMBER: NCT00842712.

Reference Dosimetry according to the New German Protocol DIN 6800-2 and Comparison with IAEA TRS 398 and AAPM TG 51.

The preceding DIN 6800-2 (1997) protocol has been revised by a German task group and its latest version was published in March 2008 as the national standard dosimetry protocol DIN 6800-2 (2008 March). Since then, in Germany the determination of absorbed dose to water for high-energy photon and electron beams has to be performed according to this new German dosimetry protocol. The IAEA Code of Practice TRS 398 (2000) and the AAPM TG-51 are the two main protocols applied internationally. The new German version has widely adapted the methodology and dosimetric data of TRS-398. This paper investigates systematically the DIN 6800-2 protocol and compares it with the procedures and results obtained by using the international protocols. The investigation was performed with 6 MV and 18 MV photon beams as well as with electron beams from 5 MeV to 21 MeV. While only cylindrical chambers were used for photon beams, the measurements of electron beams were performed by using cylindrical and plane-parallel chambers. It was found that the discrepancies in the determination of absorbed dose to water among the three protocols were 0.23% for photon beams and 1.2% for electron beams. The determination of water absorbed dose was also checked by a national audit procedure using TLDs. The comparison between the measurements following the DIN 6800-2 protocol and the TLD audit-procedure confirmed a difference of less than 2%. The advantage of the new German protocol DIN 6800-2 lies in the renouncement on the cross calibration procedure as well as its clear presentation of formulas and parameters. In the past, the different protocols evoluted differently from time to time. Fortunately today, a good convergence has been obtained in concepts and methods.

Reference Dosimetry according to the New German Protocol DIN 6800-2 and Comparison with IAEA TRS 398 and AAPM TG 51*

The preceding DIN 6800-2 (1997) protocol has been revised by a German task group and its latest version was published in March 2008 as the national standard dosimetry protocol DIN 6800-2 (2008 March). Since then, in Germany the determination of absorbed dose to water for high-energy photon and electron beams has to be performed according to this new German dosimetry protocol. The IAEA Code of Practice TRS 398 (2000) and the AAPM TG-51 are the two main protocols applied internationally. The new German version has widely adapted the methodology and dosimetric data of TRS-398. This paper investigates systematically the DIN 6800-2 protocol and compares it with the procedures and results obtained by using the international protocols. The investigation was performed with 6 MV and 18 MV photon beams as well as with electron beams from 5 MeV to 21 MeV. While only cylindrical chambers were used for photon beams, the measurements of electron beams were performed by using cylindrical and plane-parallel chambers. It was found that the discrepancies in the determination of absorbed dose to water among the three protocols were 0.23% for photon beams and 1.2% for electron beams. The determination of water absorbed dose was also checked by a national audit procedure using TLDs. The comparison between the measurements following the DIN 6800-2 protocol and the TLD audit-procedure confirmed a difference of less than 2%. The advantage of the new German protocol DIN 6800-2 lies in the renouncement on the cross calibration procedure as well as its clear presentation of formulas and parameters. In the past, the different protocols evoluted differently from time to time. Fortunately today, a good convergence has been obtained in concepts and methods.

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program.

INTRODUCTION: Pemetrexed has established efficacy, and is the backbone for chemotherapy in patients with malignant pleural mesothelioma (MPM). An International Expanded Access Program provided >3000 mesothelioma patients with access to single-agent pemetrexed or pemetrexed plus platinum analogs (cisplatin or carboplatin) in 13 countries. In this article, we report the safety and efficacy data of MPM patients who were treated with single-agent pemetrexed (n = 812). METHODS: Patients with histologically confirmed MPM, not amenable to curative surgery, received pemetrexed (500 mg/m) once (day 1) every 21 days with standard premedication and vitamin supplementation. Investigator-determined response and survival data were recorded at the end of study participation. Myelosuppression data were also collected. RESULTS: All 812 MPM patients (319 chemonaïve; 493 pretreated) received single-agent pemetrexed (>or=1 dose) and were evaluated for safety. A total of 643 patients (247 chemonaïve, 396 pretreated) were evaluated for efficacy. Of the chemonaïve patients evaluated for efficacy (n = 247), the overall response rate was 10.5%, median time to progressive disease (TTPD) was 6.0 months, and median survival was 14.1 month. Of the pretreated patients evaluated for efficacy (n = 396), the overall response rate was 12.1%, median TTPD was 4.9 months, and the median survival was not estimable due to high censoring. Common terminology criteria grade 3/4 hematologic toxicity was mild in both groups, with neutropenia (<18%) as the main toxicity. CONCLUSIONS: In the present expanded access program, single-agent pemetrexed demonstrated promising activity in MPM in both chemonaïve and pretreated patients, with TTPD of 6.0 and 4.9 months, respectively, 1-year survival >or=54.7%, and mild hematologic toxicity.

A randomized, blinded, prospective trial to compare the safety and efficacy of three bowel-cleansing solutions for colonoscopy (HSG-01*).

BACKGROUND AND STUDY AIMS: There are conflicting data regarding the optimal bowel preparation for colonoscopy. This study was carried out to compare the efficacy, safety, and tolerability of three widely used bowel lavage solutions: the standard polyethylene glycol-electrolyte solution based on the GoLytely formulation (PEG-EL1; Klean-Prep); a sulphate-free PEG-EL solution based on the NuLytely formulation (PEG-EL2, Endofalk); and a sodium phosphate preparation (NaP, Fleet Phospho-Soda). PATIENT AND METHODS: A total of 185 consecutive patients scheduled for elective colonoscopy were prospectively randomly assigned to undergo pre-colonoscopic bowel cleansing with either 4 l of PEG-EL1 (n=64), 3 l of PEG-EL2 (n=59), or 90 ml of NaP (n=62). The quality of preparatory colonic cleansing for each segment from the rectum to the ascending colon was scored on a five-level rating scale (1, very good to 5, very poor) by endoscopists who were blinded with regard to the type of preparation used. The primary outcome measure for the comparison of treatments was the "worst" score in any of the rated bowel segments. Safety and tolerability were evaluated by means of a symptom questionnaire completed by each patient immediately before the procedure. RESULTS: Of the 185 patients who were randomly assigned to one of the three treatments, 175 underwent colonoscopy and 173 were evaluable with regard to efficacy - 59, 54, and 60 patients treated with PEG-EL1, PEG-EL2, and NaP, respectively. The treatment groups were comparable with regard to the baseline characteristics. PEG-EL1 was statistically significantly superior to the other treatments in relation to the "worst cleansing" score ( P

Chemotherapy as treatment of primary and recurrent small cell lung cancer.

Chemotherapy is the treatment of choice in metastatic stage of small-cell lung cancer (SCLC). Radiation therapy, surgery and other forms of therapy are only included in special treatment situations, particularly for different local problems. A wide range of chemotherapeutic agents have proven to be effective in SCLC, including carboplatin, cisplatin, cyclophosphamide, doxorubicin, epirubicin, etoposide, ifosfamide, teniposide and vincristine. However, treatment results could not be improved over the last 10 years and the median survival of patients with metastatic disease is limited to 7-10 months. New agents like docetaxel, gemcitabine, irinotecan, paclitaxel, topotecan and vinorelbine have shown promising results in phase-II investigations. Yet, no evidence is provided from randomized trials to employ these drugs in first line treatment. Clearly, polychemotherapy is superior to single agent treatment. Compared to the combination of cisplatin and etoposide, no other combination has clearly shown improved results in large phase-III randomised trials, yet. The combination of cisplatin and irinotecan has also shown promising results in a single randomised trial with the need to be confirmed in larger settings. Neither extending the initial treatment beyond the median number of six cycles, nor maintenance treatment have-so far-resulted in any increase in survival results for patients with metastasised SCLC. Nor has dose-intensification, which causes significantly higher toxicities in patients, shown a clear impact on the overall survival of these patients. Brain metastases represent a high frequent complication associated with SCLC. In these cases, the combination of chemotherapy and whole brain radiation therapy is advocated. Second-line treatment should always be considered in patients with relapse or failure to first-line therapy. In addition to a rechallenging with the prior drug combination or selecting a different potentially non-cross resistant one, monotherapy with topotecan proved to be effective as well. In summary, up to now, no standard chemotherapy combination exists for metastatic SCLC. The individual therapy strategy can only be selected by considering the clinically relevant conditions of the patient.

Combination Chemotherapy with Docetaxel and Carboplatin for Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Docetaxel has shown promising single-agent activity in non-small cell lung cancer (NSCLC) and its activity can be enhanced by the addition of platinum compounds. Several studies indicate that carboplatin may be as effective as cisplatin but with better tolerability. OBJECTIVE: A phase II study was performed to investigate the safety and efficacy of combination chemotherapy with docetaxel and carboplatin in patients with advanced NSCLC. PATIENTS AND METHODS: 30 chemotherapy-naïve patients with stage IIIB and IV NSCLC were treated with docetaxel 90 mg/m(2) over 1 hour, followed by carboplatin administered according to a target area under the curve of 5 mg/ml/min (Calvert's formula). Treatment was repeated every 3 weeks for 6 cycles. RESULTS: Myelosuppression was the predominant toxicity. Grade 3 or 4 granulocytopenia occurred in 77% of the patients. However, granulocyte colony-stimulating factor (G-CSF) was not utilised and neutropenic fever did not occur. Grade 3 or 4 nail disorder developed in 27% of the patients. Other non-haematological toxicities, including fluid retention, were mild to moderate. The objective response rate was 30% (two complete and seven partial responses). The median time to progression was 24 weeks and median survival 57 weeks. One-year survival was 56%. CONCLUSIONS: The combination of docetaxel and carboplatin appears to be well tolerated and active in patients with advanced NSCLC.

Slow oscillations of cytochrome oxidase redox state and blood volume in unanesthetized cat and rabbit cortex. Interhemispheric synchrony.

The purpose of this study was to determine the frequency characteristics and the degree of interhemispheric synchrony of slow (< 0.5 Hz), spontaneous oscillations of the regional cortical cytochrome oxidase redox state (CYT) and blood volume (CBV) in unanesthetized animals. We implanted bilateral cortical windows and electrodes for polysomnography in 7 cats and 3 rabbits. The animals were atraumatically restrained during multiple 3-6 hour sessions for up to 8 weeks, and relative changes in the cortical CYT and CBV were monitored by dual wavelength reflectance spectrophotometry at 603 nm and 590 nm. Continuous oscillations of CYT and CBV, unrelated to pulse or respiration, were always observed in each animal. Frequency (FFT) analysis over time revealed a nonstationary distribution of frequencies below 0.4 Hz, with most of the spectral power being contained in the 0-0.25 Hz band during both waking and sleep. Although the time-frequency plots of the CYT and CBV signals were similar, an occasional dissociation between the CYT and CBV oscillations was found. Analysis of simultaneous bilateral cortical optical recordings revealed a significant and sustained interhemispheric cross-correlation over time between the CYT as well as the CBV oscillations during stable recordings as long as 60 min. We conclude that: 1) CYT and CBV levels normally oscillate at < 0.4 Hz in the unanesthetized cat and rabbit cortex; 2) these complex oscillations, whose frequencies are non-stationary over time, nevertheless show sustained interhemispheric synchrony between 50 mm2 homotopic cortical regions; and 3) these oscillations may in part represent fluctuations of the metabolic rate.

Chemotherapy-induced severe thrombocytopenia in gynecologic oncology and its treatment with interleukin-3.

Six patients suffering from various gynecologic malignancies developed severe thrombocytopenia (WHO IV) after normal-dose chemotherapy. All patients were treated with platelet transfusions but the results on hematopoietic recovery were not satisfactory. Therefore treatment with a new hematopoietic substance (rh interleukin-3) was initiated. All patients received a dosage of 5 mu g/kg/bw daily s.c. up to 10 days depending on the response of platelet counts. In two women, who had suffered from severe hemorrhage (epistaxis resp. ankle joint hematoma), symptoms disappeared after approximately three days of rhIL-3 use. Whereas platelet transfusions were ineffective in all patients, IL-3 led to a significant increase of the platelet count after 3-5 days of application. Side-effects were mild, when seen in one case, where G-CSF was given at the same time. Our experience supports the idea of using new growth factors like rhIL-3 to cure chemotherapy-induced myelosuppression, such as severe thrombocytopenia.

Interhemispheric synchrony of slow oscillations of cortical blood volume and cytochrome aa3 redox state in unanesthetized rabbits.

In order to study spontaneous, slow oscillations of regional oxidative metabolism and blood flow in the normal, unanesthetized cortex, adult rabbits were implanted with bilateral cortical windows and electrodes for polysomnography. Relative changes in the cortical intramitochondrial redox state of cytochrome aa3 (CYT) and blood volume (CBV) were monitored by dual-wavelength reflectance spectrophotometry. Continuous, non-stationary oscillations (< 0.5 Hz) of both CYT and CBV were observed during waking and non-REM sleep. Cross-correlation analysis revealed a predominant interhemispheric synchrony of these oscillations which were unrelated to the heart rate, breathing, or electrocorticogram pattern. These findings suggest a dynamic linkage of slowly varying metabolic and vascular processes between unanesthetized cortical regions of 50 mm2 surface area.

An automated high capacity data capture and analysis system for the in vitro assessment of leukocyte adhesion under shear-stress conditions.

Parallel-plate flow chambers have been used to model the vascular microcirculation and study the in vitro dynamic adhesive interactions of leukocytes and human umbilical vein endothelial cells (HUVECs). We describe here a high capacity system which can simultaneously monitor the adhesive interaction of neutrophils and HUVECs in ten flow chambers. Automated data collection was achieved with an image analyzer controlling the autostage and autofocus attachments of an inverted microscope. Images from the flow chambers were captured via phase-contrast microscopy using a video camera and laser videodisk recorder. The images were downloaded off-line into an image analyzer for automated counting of rolling and adherent cells. Neutrophils were detected by their "phase bright' characteristics. An automated optimization procedure allowed the computer to choose the best setting for the selective detection of neutrophils. In addition, a method which utilized image averaging was used to distinguish between rolling and adherent cells. A comparison of the results obtained from the manual and automated counting methods revealed linear relationships for the counting of both adherent (r = 0.98) and rolling cells (r = 0.96) with counting efficiencies of 59% and 46%, respectively. The utility of the system was demonstrated by its ability to measure the adhesive interaction between neutrophils and HUVEC in response to stimulus such as interleukin-1 alpha (IL-1 alpha), histamine, or formyl-1-methionyl-1-leucyl-1-phenylalanine (fMLP). In conclusion, we have developed an automated assay which combines the capacity of ten flow chambers with a computerized data analysis system; the result is an efficient and reproducible assay which minimizes operator associated errors and biological variability.

Apparent unilateral visual neglect in MPTP-hemiparkinsonian monkeys is due to delayed initiation of motion.

Monkeys made hemiparkinsonian by infusion of a solution of MPTP into one carotid artery appeared to ignore food presented from the contralateral side. Initial observations suggested neglect of visual stimuli presented as fruit treats by automated delivery system in the half-field contralateral to MPTP treatment. Further studies in which fruit treats were left in the 'neglected' visual field indicated that this apparent neglect, unlike neglect attending cortical lesions, was rather a marked delay in initiating movements (unilateral hypokinesia). These observations may explain apparent subcortical neglect and are consistent with the known role of nigrostriatal dopaminergic neurones in movement regulation. This is a useful animal model in which difficulties in initiation of movement (hypokinesia). a cardinal symptom of Parkinson's disease, can be studied separately from other deficits in motor performance.

Flow cytometric analysis of platelet surface antigens.

A flow cytometric analysis of human platelet surface antigens was carried out using a panel of monoclonal antibody reagents. The reagents used were specific either for the GPIb or the GP IIb/IIIa complex, surface immunoglobulin, or von Willebrand factor (vWf). Indirect surface immunophenotypes were determined using an EPICS V flow cytometer and the monoclonal antibodies 6D1, 10E5, Plt-1, UR1663, anti-IgG, and anti-vWf. Platelets were obtained from normal individuals or patients with either Bernard-Soulier syndrome (BSS) or Glanzmann's thrombasthenia (GT). Normal platelets were positive for 10E5, 6D1, Plt-1, and UR1663 and showed negligible activity for anti-IgG and anti-vWf. Platelets from individuals with BSS showed a marked reduction in 6D1, while the platelets of a patient with GT showed a marked reduction in binding of 10E5, Plt-1, and UR1663. Differences between histograms for normal platelets and for platelets from individuals with BSS or GT were evaluated using the Kolmogorov-Smirnov test. Compared to normal platelets, the BSS and GT platelets contain at least 35-fold less of the GPIb and GP IIb/IIIa complex respectively. Flow cytometry is a useful and precise method for the study of normal and abnormal surface platelet phenotypes.

Low-frequency oscillations of cortical oxidative metabolism in waking and sleep.

To study the changes in cortical oxidative metabolism and blood volume during behavioral state transitions, we employed reflectance spectrophotometry of the cortical cytochrome c oxidase (cyt aa3) redox state and blood volume in unanesthetized cats implanted with bilateral cortical windows and EEG electrodes. Continuous oscillations in the redox state and blood volume (approximately 9/min) were observed during waking and sleep. These primarily metabolic oscillations of relatively high amplitude were usually synchronous in homotopic cortical areas, and persisted during barbiturate-induced electrocortical silence. Their mean amplitude and frequency did not vary across different behavioral/EEG states, although the mean levels of cyt aa3 oxidation and blood volume during rapid eye movement (REM) sleep significantly exceeded those during waking and slow-wave sleep. These data suggest the existence of a spontaneously oscillating metabolic phenomenon in cortex that is not directly related to neuroelectric activity. A superimposed increase in cortical oxidative metabolism and blood volume occurs during REM sleep. Experimental data concerning cerebral metabolism and blood flow that are obtained by clinical methods that employ relatively long sample acquisition times should therefore be interpreted with caution.

A system for measuring the angular response of hemiparkinsonian monkeys to a food stimulus.

A Zenith Z-100 PC system was used to control an automated feeding system for determining the angular limits at which a monkey would respond to a food stimulus. Raisins secured to the end of a rotating arm by means of vacuum pressure were delivered to the monkey alternately from clockwise and counterclockwise directions at a fixed radius. The point at which the monkey took a raisin from the end of the arm was determined by an increase in negative pressure. The arm position was measured by using a potentiometer mounted in the arm gear train. The computer system controlled the experiment as well as the on-line recording and plotting of data.

A simplified method for monitoring the cytochrome aa3 redox state in bilateral cortical areas of unanesthetized cats.

We describe a versatile optical system that enables the simultaneous monitoring of the redox state of cytochrome c oxidase (cytochrome aa3) in two homologous cortical areas under chronically implanted windows in cats. A single light source, broad bandpass primary filters, light-conducting rods, and narrow-bandpass interference detecting filters are employed. We observed reproducible responses of the cytochrome redox state and blood volume to carotid occlusion and terminal anoxia during anesthesia, and to graded doses of pentobarbital in awake animals.