Biomedical subjects

K Kranda

Publications and source records attributed to K Kranda.

At least 19 recordsLinked to original sources

PubMed2005

Antibody formation against beta-tubulin class III in response to brain trauma.

Brain trauma typically leads to neuronal damage and loss. Assuming a transient autoimmune response to debris of the damaged neurones, we have monitored serum titres of IgG and IgM antibodies to beta-tubulin class III (betaTcIII), which is almost exclusively found in neuronal cytoskeletons. In 15 out of 18 patients, the peak of the IgG or IgM antibody titre appeared in the serum within 3 weeks of a brain trauma.

Antibody Formation↗

PubMed2001

A prospective study of 2-[18F] fluoro-2-deoxy-D-glucose/positron emission tomography scan, 99mTc-labeled arcitumomab (CEA-scan), and blind second-look laparotomy for detecting colon cancer recurrence in patients with increasing carcinoembryonic antigen levels.

BACKGROUND: An increasing carcinoembryonic antigen (CEA) level in the absence of disease on imaging studies can present a diagnostic challenge. We evaluated 2-[18F] fluoro-2-deoxy-D-glucose and positron emission tomography (FDG-PET) scan and CEA scan before second-look laparotomy as a means of localizing recurrent colorectal cancer. METHODS: Patients underwent computed tomography scan, bone scan, colonoscopy, and magnetic resonance imaging, and those without evidence of disease or resectable disease in the abdomen had FDG-PET and CEA scans. At second-look laparotomy, a surgeon blinded to the results of the FDG-PET and CEA scans performed an exploration and mapped findings. A second surgeon, with knowledge of the FDG-PET and CEA scans, then explored the patient; all lesions were biopsied or resected for pathology. RESULTS: In 28 patients explored, disease was found at operation in 26 (94%). Ten had unresectable disease. FDG-PET scans predicted unresectable disease in 90% of patients. CEA scans failed to predict unresectable disease in any patient. In 16 patients found to have resectable disease or disease that could be treated with regional therapy, FDG-PET scan predicted this in 81% and CEA scan in 13%. CONCLUSIONS: FDG-PET scan can predict those patients who would likely benefit from a laparotomy. If the FDG-PET scan indicates resectable disease, laparotomy can be considered. However, if the findings predict unresectable disease or the absence of disease, the patient should pursue systemic therapy or continued observation.

Adult↗

PubMed1998

Preoperative tumor volume is associated with outcome in malignant pleural mesothelioma.

OBJECTIVES: Our objective was to analyze the impact of preoperative and postresection solid tumor volumes on outcomes in 47 of 48 consecutive patients undergoing resection for malignant pleural mesothelioma who were treated prospectively and randomized to photodynamic therapy or no photodynamic therapy. METHODS: From July 1993 to June 1996, 48 patients with malignant pleural mesothelioma had cytoreductive debulking to 5 mm or less residual tumor by extrapleural pneumonectomy (n = 25) or pleurectomy/decortication (n = 23). Three-dimensional computed tomographic reconstructions of preresection and postresection solid tumor were prospectively performed and the disease was staged postoperatively according to the new International Mesothelioma Interest Group staging. RESULTS: Median survival for all patients is 14.4 months (extrapleural pneumonectomy, 11 months; pleurectomy/decortication, 22 months; p2 = 0.07). Median survival for preoperative volume less than 100 was 22 months versus 11 months if more than 100 cc, p2 = 0.03. Median survival for postoperative volume less than 9 cc was 25 months versus 9 months if more than 9 cc, p2 = 0.0002. Thirty-two of forty-seven (68%) had positive N1 or N2 nodes. Tumor volumes associated with negative nodes were significantly smaller (median 51 cc) than those with positive nodes (median 166 cc, p2 = 0.01). Progressively higher stage was associated with higher median preoperative volume: stage I, 4 cc; stage II, 94 cc; stage III, 143 cc; stage IV, 505 cc; p2 = 0.007 for stage I versus II versus III versus IV. Patients with preoperative tumor volumes greater than 52 cc had shorter progression-free intervals (8 months) than those 51 cc or less (11 months; p2 = 0.02). CONCLUSIONS: Preresection tumor volume is representative of T status in malignant pleural mesothelioma and can predict overall and progression-free survival, as well as postoperative stage. Large volumes are associated with nodal spread, and postresection residual tumor burden may predict outcome.

Combined Modality Therapy↗

PubMed1997

Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma.

BACKGROUND: Patients with malignant pleural mesothelioma (MPM) usually die of progressive local disease. This report describes the results of a Phase III trial comparing maximum debulking surgery and postoperative cisplatin, interferon alpha-2b, and tamoxifen (CIT) immunochemotherapy with and without intraoperative photodynamic therapy (PDT) to determine (1) whether such a multimodal approach can be performed with minimum morbidity and mortality in malignant pleural mesothelioma (MPM), and (2) whether first-generation (i.e., 630-nm laser light, Photofrin II) intrapleural PDT impacts on local recurrence of survival. METHODS: From July 1993 to June 1996, 63 patients with localized MPM were randomized to either PDT or no PDT. The tumors of 15 patients could not be debulked to 5 mm. Patients assigned to PDT (n = 25) and no PDT (n = 23) were similar with respect to age, sex, tumor volume, and histology. RESULTS: The type of resection (11 pleurectomies and 14 pneumonectomies vs. 12 pleurectomies and 11 pneumonectomies), length postoperative stay, and ICU time were comparable (PDT vs. no PDT). There was one operative death (hemorrhage), and each group had two bronchopleural fistulas. Postoperative staging divided patients into the following categories: stage I: PDT, 2, no PDT, 2; stage II: PDT, 2, no PDT, 2; stage III, PDT, 21; no PDT, 17; stage IV, PDT, 0; no PDT, 2. Comparable numbers of CIT cycles were delivered. Median survival for the 15 non-debulked patients was 7.2 months, compared to 14 months for the 48 patients on protocol. There were no differences in median survival (14.4 vs. 14.1 months) or median progression-free time (8.5 vs. 7.7 months), and sites of first recurrence were similar. CONCLUSIONS: Aggressive multimodal therapy can be delivered for patients with higher stage MPM. First-generation PDT does not prolong survival or increase local control for MPM.

Adult↗

PubMed1996

Processing visual evoked potentials based on matched filtering of single trial responses.

Physiological signals recorded after presentation of a stimulus can be considered as the sum of an evoked sensory response and uncorrelated noise corresponding to the spontaneous neural background activity. In case of low signal-to-noise ratio, the sensory signal is estimated by averaging a large number of single trial records sampled under the same experimental conditions. The averaging technique, however, is inappropriate for displaying trial-to-trial variations that may occur during a recording session. A method based on matched filtering was developed for processing single visual evoked potentials (VEPs). To illustrate the performance of this method, a set of VEPs for grating patches of 8 different contrasts (including 0) was evaluated. The VEPs were subjected to signal detection analysis by computing for each contrast similarity indices between the single trial records and the averaged response used as a template. The signals were analysed in terms of probability density distributions, expressing the goodness of fit between template and each single waveform.

Cluster Analysis↗

PubMed1995

A phase II trial investigating primary immunochemotherapy for malignant pleural mesothelioma and the feasibility of adjuvant immunochemotherapy after maximal cytoreduction.

BACKGROUND: The treatment of malignant pleural mesothelioma (MPM) continues to be inadequate with the use of standard techniques, including surgery, radiotherapy and chemotherapy. We initiated a phase II trial of immunochemotherapy with cisplatinum (25 mg/m2 four times weekly), interferon-alpha (5 mU/m2 s.c. three times weekly, and tamoxifen (20 mg orally twice a day for 35 days) (CIT) based on in vitro and in vivo data suggesting interrelating efficacy of this combination. METHODS: Since July 1991, 36 patients have been evaluable for response after receiving one to five cycles of CIT. Ten additional patients had debulking surgery followed by two cycles of postoperative adjuvant CIT commencing a mean of 6 weeks after surgery. RESULTS: Toxicity was acceptable (4% grade III/IV). One treatment-related death (2%) occurred, from myocardial infarction. A 19% partial response rate, objectively quantified using three-dimensional computerized tomographic (CT) measurement of solid disease volume, was recorded. The median survival for the seven responders was 14.7 months, whereas that of the nonresponders was 8 months (p2 = 0.2). Median survival for the entire group was 8.7 months. Preoperative size, platelet count > 360,000/ml, and nonepithelial histology were associated with shortened survival. CONCLUSIONS: The CIT regimen has some activity in MPM and can be delivered after debulking resection. In good-risk patients, as defined by favorable prognostic factors, a randomized trial using this combination may be warranted.

Adult↗

PubMed1994

Isolated lung perfusion with tumor necrosis factor: a swine model in preparation of human trials.

Isolated lung perfusion with tumor necrosis factor (TNF) potentially could deliver high doses of drug and avoid systemic toxicity in patients with unresectable lung cancer or metastases. We investigated the feasibility of isolated lung perfusion with TNF in a pig model. Eleven animals had left-sided isolated lung perfusion with no TNF (n = 3), 40 micrograms/kg TNF (n = 2), 80 micrograms/kg TNF (n = 3), and 40 micrograms/kg TNF at moderate (39.5 degrees C) hyperthermia (n = 3). Hemodynamic monitoring and measurement of systemic and pulmonary circuit TNF levels were performed. Surviving animals were electively sacrificed a minimum of 6 months after isolated lung perfusion. All sham-perfused pigs survived. Isolated lung perfusion elevated pulmonary artery pressure, decreased cardiac output, and had minimal effects on mean pressure (15 +/- 0 versus 32 +/- 8 mm Hg, 4.5 +/- 1.1 versus 3.03 +/- 0.03 L/min, 67 +/- 11 versus 61 +/- 2 mm Hg; before versus after 90 minutes of isolated lung perfusion). Both 40 micrograms/kg animals and 2 of the 3 hyperthermic perfusion pigs survived, with 1 requiring pneumonectomy. Of the three 80 micrograms/kg animals, 1 survived, 1 died, and 1 required pneumonectomy. Survivors, compared with dying animals, had lower systemic/pulmonary TNF ratios and lower peak systemic TNF levels. All surviving pigs were electively sacrificed. These data justify phase I human protocols of isolated lung perfusion with TNF and hyperthermia; however, intraoperative leak rates must be monitored to ensure pulmonary isolation because systemic TNF levels may dictate treatment morbidity/mortality.

Animals↗

PubMed1984

Are the amplitudes of visual evoked potentials sensitive indices of hangover effects after repeated doses of benzodiazepines?

Here we compared the efficacy of two electrophysiological techniques in detecting hangover effects after repeated administration (five days) of benzodiazepines. Twelve hours after the last ingestion, possible effects on evoked potentials (EPs) of the long- and short-acting benzodiazepines, flurazepam and lormetazepam, were compared here with those of placebo under a double-blind experimental condition. The EPs were recorded from occipital and parietal sites during an active discrimination of two amoeboid shapes and passive viewing of sine-wave grating patterns turned on and off. In the former task, the subject was requested to make a selective response with respect to whether the two shapes appeared the same or different and his reaction times were simultaneously recorded. Neither benzodiazepine influenced the latencies of any of the sensory and late EP components. Flurazepam's long-acting metabolite, N-desalkylflurazepam, reduced the amplitudes of all the EP components suggesting a somewhat general mode of action. This was not the case for lormetazepam. N-desalkylflurazepam reduced the amplitudes of the occipital visual evoked potentials (VEPs) to sine-wave gratings to a greater extent than the amplitudes of the late parietal EPs to amoeboid shapes. This effect did not show any particular preference for either of the subsystems processing pattern and movement information. The amplitudes of the late EP components, such as N200 and P300 waves recorded from parietal sites, were reduced considerably more after flurazepam administration than their counterparts recorded from the occiput. This observation points to the possible existence of at least two separate sources of the N200-P300 complex with different affinities to the N-desalkylflurazepam. The flurazepam-induced amplitude reduction observed for VEPs to gratings may reflect an attenuation in the detectability of both pattern and movement. The attenuation of the late EP amplitudes is possibly a function of several processes, one of which is conceivably the anxiolytic property of flurazepam which lowers the level of the activation state and this in turn is known to contribute to the amplitude size of the N200-P300 complex.

Adult↗

PubMed1984

What can colour thresholds tell us about the nature of the underlying detection mechanisms?

Two-colour increment thresholds, which have traditionally been analysed in terms of pi-mechanisms, were subjected here to a different form of analysis. Detection thresholds were measured for monochromatic test flashes and 10 bichromatic mixture combinations containing various proportions of two out of the five primaries: white, blue, green, yellow and red. The 1 degree, 0.5-s duration, foveal flashes appeared on a 1000-td blue background. All the thresholds were simultaneously fitted by assuming probability summation from a limited number of independent linear mechanisms. The assumption of two detection mechanisms provided a reasonable fit for all the bichromatic mixture thresholds. One mechanism received a positive contribution from both M and L cone types, whereas the other received an excitatory contribution from the L cone type, and an inhibitory contribution from the M cone type. The predictive power of the model was tested and compared to the pi-mechanism concept by fitting a spectral-sensitivity curve measured under identical conditions. It was concluded that parts of pi-mechanism curves probably reflect the responses of colour-opponent processes rather than those of single cone types.

Color Perception↗

PubMed1983

Effects of intraoperative electron irradiation in the dog on cell turnover in intact and surgically-anastomosed aorta and intestine.

Adult dogs were subjected to laparotomy and intraoperative electron irradiation after division and reanastomosis of aorta or after construction of a blind loop of small intestine having a transverse suture line and an end-to-side anastomosis. Dogs received intraoperative irradiation of both intact and anastomosed aorta or intestine in doses of 0, 2000, 3000, or 4500 rad. Animals were sacrificed at seven days or three months following treatment. At 24 hours prior to sacrifice, dogs received 5 mCi tritiated thymidine intravenously. Irradiated and non-irradiated segments of aorta and small intestine, including intact and anastomotic regions, were analyzed for tritiated thymidine incorporation and were subjected to autoradiography. Incorporation studies showed diminution in tritiated thymidine uptake by irradiated portions of aorta and small intestine, in both intact and anastomotic regions. Autoradiograms revealed that irradiated areas of intact or anastomotic aorta or intestine had diminished labeling of stromal cells, suggesting a lowered cell proliferative capacity of irradiated tissue compared to non-irradiated portions. Inflammatory cells showed similar labeling indices in irradiated and non-irradiated tissues, both intact and surgically-manipulated, suggesting that irradiation does not significantly affect a subsequent local inflammatory response. Radiation-induced decreases in tritiated thymidine incorporation in irradiated aorta and small intestine were generally more marked at seven days than at three months following irradiation, suggesting that radiation-induced depression of cell turnover rates decreases with time. The presence of tritiated thymidine uptake after irradiation demonstrates the ability of intact and surgically-manipulated aorta and intestine to recover from radiation-induced damage.

Animals↗

PubMed1983

Analysis of reaction times to coloured stimuli.

Reaction times were measured for 10- and 500-ms coloured stimuli at three different threshold intensity levels. The stimulus intensity of a 1 degree foveal flash detected with a probability of 0.5 was taken as the threshold intensity level. All flashes were superimposed on a 1000-td white background. The reaction time distributions were classified in terms of sustained- and transient-like responses. The distributions for the 0.5-s blue, red and white flashes all appear sustained-like at the subthreshold and threshold intensity levels. As the blue, red and white flashes were probably detected by different systems (colour-opponent and luminance) it appears that the sustained-like response is not a prerogative of any particular detection system. The responses to the blue flashes are on average about 80 ms longer than those to the white and red flashes. This difference can be attributed to a somewhat slower operation of either the blue-sensitive cones or of the blue/yellow opponent system. The responses to the white 10-ms flashes are about 120 ms faster than those to the 500-ms flashes. This considerable difference may reflect the faster response of the transient system.

Color Perception↗

PubMed1981