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Biomedical subjects

P Lindholm

Publications and source records attributed to P Lindholm.

At least 19 recordsLinked to original sources
PubMed2006

Loss of motor control and/or loss of consciousness during breath-hold competitions.

Since the first official world championships in breath-hold diving (1996), a sport has developed where the athletes compete in various disciplines of breath-hold diving. One of the rules is that the diver should surface from a dive without showing any signs of hypoxia. Depending on the severity of hypoxia, a diver may suffer disqualifying signs such as loss of consciousness (LOC) or loss of motor control (LMC), the latter including signs such as confusion, affected postural control, spasms or speech problems. Data was collected from the results of the major international competitions following AIDA guidelines (Association International pour le Dévelopment de l'Apnée) in 1998, 2001-2004. The data was analyzed for frequency of LOC and LMC during constant weight diving and during static apnea. In constant weight diving, the diver swims down (and up) as deeply as possible along a vertically suspended rope (current record 105 m). In static apnea, the diver strives for maximum duration, floating motionless face down in a pool (current record 8.58 min). A total of 601 static apnea (SA) performances and 596 constant weight dives were judged in the six competitions. On average, 10 % of SA, and 11 % of CW performances were disqualified due to signs of hypoxia. For the competitions in 2002-2004, a distinction was made in the rules between LOC and LMC; of a total number of 355 SA performances, 1.1 % resulted in LOC, while 9.6 % resulted in LMC. For CW, the number was 344 with 6.1 % LOC and 6.1 % LMC. Despite the relatively high incidence of dramatic signs, it is noteworthy that there have been no reports of fatal accidents or permanent injuries from any of the above-mentioned competitions. This descriptive paper shows a relatively high incidence of disqualifications due to signs of hypoxia in breath-hold competitions 1998-2004.

Competitive Behavior↗
PubMed2006

Time components of circulatory transport from the lungs to a peripheral artery in humans.

Blood gas changes occurring in the lung undergo delay and damping on their way to a peripheral artery sampling site. Knowledge of the time components of circulatory transfer is important for the understanding of respiratory control and cardiovascular reflexes in response to blood gas transients. Providing steady state with regard to VA/Q distribution, cardiac output and peripheral blood flow, the relationship between the time courses of small end-tidal and peripheral PO2 changes is determined by the transfer function of the interposed vascular segment. This transfer function, expressed as delay time TD and mean transit time (MTT), was measured in six well-trained subjects, allowing the calculation of arterial time-courses from end-tidal to the reverse. They were studied at rest and during four different dynamic leg exercise intensities in the supine posture. TD and MTT amounted to 15.8 +/- 1.7 (mean +/- SEM) and 18.3 +/- 2.1 s at rest and were shortened to 7.7 +/- 0.6 and 11.5 +/- 1.8 s during exercise at 170 W. The shortening of TD and MTT did not appear to be simply an inverse function of cardiac output, suggesting that the shortening occurs in the central circulatory segment but not in the arm segment.

Adult↗
PubMed2006

Effects of IKK inhibitor PS1145 on NF-kappaB function, proliferation, apoptosis and invasion activity in prostate carcinoma cells.

A key antiapoptotic transcription factor, nuclear factor kappa-B (NF-kappaB), is known to be critically important for tumor cell growth, angiogenesis and development of metastatic lesions. We and others showed previously that NF-kappaB transcription factor was constitutively activated in androgen-independent prostate carcinoma (PC) cell lines due to the upregulated activity of inhibitor of NF-kappaB kinases (IKK). In this work, using luciferase assay, electrophoretic mobility shift assay and Northern blot analysis of expression of endogenous kappaB-responsive genes, we demonstrate that a novel highly specific small-molecule IKK inhibitor, PS1145, efficiently inhibited both basal and induced NF-kappaB activity in PC cells. We found that PS1145 induced caspase 3/7-dependent apoptosis in PC cells and significantly sensitized PC cells to apoptosis induced by tumor necrosis factor alpha. We also showed that PS1145 inhibited PC cell proliferation. Effects of PS1145 on proliferation and apoptosis correlated with inhibition of interleukin (IL)-6, cyclin D1, D2, inhibitor of apoptosis (IAP)-1 and IAP-2 gene expression and decreased IL-6 protein level. In addition, we found that incubation with PS1145 inhibited the invasion activity of highly invasive PC3-S cells in invasion chamber assay in a dose-dependent manner. Overall, this study provides the framework for development of a novel therapeutic approach targeting NF-kappaB transcription factor to treat advanced PC.

Animals↗
PubMed2003

Small, novel proteins from the mistletoe Phoradendron tomentosum exhibit highly selective cytotoxicity to human breast cancer cells.

Four novel proteins (phoratoxins C-F) have been isolated from the North American mistletoe Phoradendron tomentosum. The amino acid sequences of these phoratoxins were determined unambiguously using a combination of Edman degradation and trypsin enzymatic digestion, and by electrospray ionization tandem mass spectrometry sequencing. Phoratoxins C, E and F consist of 46 amino acid residues; and phoratoxin D of 41. All proteins had six cysteines, similar to the earlier described phoratoxins A and B, which are thionins. The cytotoxicity of each protein was evaluated in a human cell line panel that represented several cytotoxic drug-resistance mechanisms. For the half-maximal inhibitory concentrations (IC50 values) of the different cell lines in the panel, correlation with those of standard drugs was low. The most potent cytotoxic phoratoxin C was further tested on primary cultures of human tumor cells from patients. The solid tumor samples from breast cancer cells were 18 times more sensitive to phoratoxin C than the tested hematological tumor samples.

Amino Acid Sequence↗
PubMed2003

A retrospective quantitative assessment of breast sensation after lateral pedicle mammaplasty.

Preservation of sensitivity is one of the important objectives in reduction mammaplasty. The lateral or medial pedicle reduction mammaplasty technique aims to maintain superficial innervation of the breast. These superficial nerves are smaller and more variable compared with deep and larger nerve structures, which are excised during this procedure. An assessment of recovery of tactile sensitivity after lateral pedicle mammaplasty was performed retrospectively. One hundred and one women, operated on between the year 1985 and 2000, with a lateral pedicle mammaplasty, were reviewed. Using a standardised questionnaire, women reported on subjective changes in sensation after surgery, including time of recovery and the influence which surgery had on sensual function. Fifty-nine of these women were tested 3-7 years after surgery. Touch sensitivity was measured using a set of 20 Semmes-Weinstein monofilaments. Erectile function was also tested. The mean pressure threshold for the areola region was 19.12 g/mm(2) and for the nipple 16.75 g/mm(2), which is better that in studies on inferior pedicle mammaplasty. In previous studies patients were tested earlier, which may explain this difference.No correlation was found between sensitivity and resected tissue (for the areola p=0.88 and for the nipple p=0.82) or between sensitivity and age of patients (for the areola p=0.73 and for the nipple p=0.80). There were individual differences in the results. It is speculated that variability in anatomy of superficial nerves might explain these differences. Nearly all patients tested regained their erectile function. The majority of patients did not notice any change in their erogenous function. Twelve (12%) reported a post-surgical improvement of sensation. Nipples with partial loss of sensation persisted in 2% of the patients.

Adult↗
PubMed2003

Lactation and breast-feeding ability following lateral pedicle mammaplasty.

A retrospective study was undertaken to evaluate the ability of breast-feeding using lateral pedicle reduction mammaplasty. A standard questionnaire was sent to 72 patients who had been operated on at a fertile age. Data was collected regarding the duration and quality of preoperative and postoperative breast-feeding, difficulties while breast-feeding, reasons for discontinuation of breast-feeding or for not attempting to breast-feed, and postoperative subjective sensitivity. Thirteen of the women who replied to the questionnaire had given birth after surgery. The pressure threshold sensitivity of areola-nipple complex was measured in nine of the above cases. To preserve lactation, a technique leaving structures untouched within the pedicle with increased dimensions was used.Breast-feeding was considered successful in this study if it was performed exclusively, without supplementation, for two months. Seven women (54%) breast-fed successfully for between two and 14 months (5.8+/-1.3) following surgery. Two women (16%) were classified as unsuccessful and four women (30%) did not breast-feed at all. The success of breast-feeding was limited by nonsurgical factors including the influence of medical personal. Five of eight women (62%) who had children preoperatively improved their rate of breast-feeding after surgery. No correlation was demonstrated between measured sensitivity and breast-feeding (p=0.65). No significant correlation was found between the resected tissue and breast-feeding (p=0.08). No relation was observed between the duration of breast-feeding and the period between operation and partus.

Adolescent↗
PubMed2001

A novel multiparametric approach for analysis of cytoplasmic immunoglobulin light chains by flow cytometry.

We describe a novel flow cytometric approach using a two-step acquisition technique to determine the cytoplasmic immunoglobulin light chains (LC) expression. Samples were prepared by a lysed-whole-blood technique and incubated with CD38-PE (phycoerythrin) and CD45-FITC (fluorescein isothiocyanate). The cells were fixed and acquired on an FACSCalibur flow cytometer (first acquisition). The cells were then permeabilized, incubated with either kappa-FITC or lambda-FITC and reacquired (second acquisition). Analysis of the data was performed by gating on the differing intensities of CD38 and evaluating them for the presence of a shifting FITC-positive population from the first acquisition to the second acquisition. The FITC fluorescence intensity of the second acquisition was equal to the sum of surface CD45 expression obtained during the first acquisition and the cytoplasmic LC expression obtained during the second acquisition. Thus, the shifting (increase) of FITC fluorescence intensity during the second acquisition is specifically due to the cytoplasmic expression of either the kappa or lambda LC. We studied 15 multiple myeloma (MM) patients and 10 controls (samples from patients without plasma cell dyscrasias). None of the controls showed evidence of any clonal populations. Thirteen of 15 MM patients exhibited clonal plasma cells (CD38 bright), ranging from 0.01% to 34% of total events collected. In addition, we identified another minute clonal population of lymphocytes (CD38 dim, CD45 bright, low forward and side scatter) in 12 of 13 MM patients with clonal plasma cells. This population, ranging from 0.01% to 0.6% of total events collected, had the same LC restriction as the clonal plasma cells. Patients with a ratio of minor clonal population to clonal plasma cells less than 0.07 tended to remain in partial or complete remission than those with a ratio > or =0.07 (4/5 versus 1/4, P <.1, chi(2)). We conclude that this method is highly sensitive and permits us to identify the minute clonal population of lymphocytes in MM patients. Our preliminary observations with a small cohort of patients imply that this minute clonal population may have important prognostic significance. The prognostic significance should be confirmed by further studies.

ADP-ribosyl Cyclase↗
PubMed2001

Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells.

The saponin digitonin, the aglycone digitoxigenin and five cardiac glycosides were evaluated for cytotoxicity using primary cultures of tumor cells from patients and a human cell line panel (representing different cytotoxic drug-resistance patterns). Of these seven compounds, proscillaridin A was the most potent (IC(50): 6.4--76 nM), followed by digitoxin, and then ouabain, digoxin, lanatoside C, digitoxigenin and digitonin. Correlation analysis of the log IC(50) values for the cell lines in the panel showed that compound cytotoxicity was only slightly influenced by resistance mechanisms that involved P-glycoprotein, topoisomerase II, multidrug resistance-associated protein and glutathione-mediated drug resistance. Digitoxin and digoxin expressed selective toxicity against solid tumor cells from patients, while proscillaridin A expressed no selective toxicity against either solid or hematological tumor cells. The results revealed marked differences in cytotoxicity between the cardiac glycosides, both in potency and selectivity, and modes of action for cytotoxicity that differ from that of commonly used anticancer drugs.

Antineoplastic Agents↗
PubMed2000

A novel human processed gene, DAD-R, maps to 12p12 and is expressed in several organs.

A cDNA of a processed gene of human DAD-1 (defender against apoptotic cell death) was cloned from the human neuroblastoma cell line SH-SY5Y. The genomic sequence of this novel processed gene, DAD-R, lacked introns and was flanked by 8 bp terminal repeats. RT-PCR showed that the transcript is expressed predominantly in testis, ovaries, pancreas, lung and skeletal muscle. DAD-R has several possible initiation codons, one of them producing an open reading frame comprising 75% of the DAD-1 gene. We determined the chromosomal localization of DAD-R as 12p11.2-12p12.1, an area linked to familial synpolydactyly and frequently amplified in a variety of cancers, including those of testis, ovaries, pancreas and lungs.

Amino Acid Sequence↗
PubMed2000

NOX 100, a nitric oxide scavenger, enhances cardiac allograft survival and promotes long-term graft acceptance.

BACKGROUND: We examined the role of nitrosative stress in allograft destruction. METHODS: Rats undergoing cardiac transplants received NOX-100, a water-soluble nitric oxide (NO) scavenger with antioxidant properties, with or without low-dose cyclosporine (CsA). Graft survival, NO production, and nuclear factor kappa B (NF-kappaB) activity were studied. RESULT: Using NOX-100 daily until rejection prolonged graft survival (11.6+/-0.6 vs. 7.4+/-0.2 days; P<0.05). Daily low-dose CsA (2.5 mg/kg im) for 7 days or until rejection also prolonged survival (12.6+/-0.5 and 21.6+/-1.6 days, respectively; P<0.01 vs. Controls). Low-dose CsA for 7 days and NOX-100 for 30 days prolonged graft survival (45.0+/-4.7 days; P<0.01 vs. all groups.). NOX-100 had no effect on whole blood CsA levels. Combination therapy until Day 100 resulted in 1 graft loss at Day 116 and indefinite survival in 3 animals (>300 days), which accepted a second WF strain heart without further immunosuppressive therapy but promptly rejected a third party (ACI) cardiac allograft. NOX-100 and CsA reduced nitrate and nitrite, and combination therapy completely normalized NO through to Day 30. Electron paramagnetic resonance spectroscopic analysis demonstrated reduction of signals for nitrosylmyoglobin and nitrosyl-heme with NOX-100 and elimination of signals with CsA alone or combination therapy. Activity of myocardial NF-kappaB decreased with monotherapy vs. untreated allografts. Combination therapy resulted in further inhibition of NF-kappaB up to Day 30. The extent of graft survival correlated with the extent of NO scavenging and NF-kappaB inhibition. Short-term combination therapy had no effect on graft lymphocytic infiltrate on Days 15, 20, and 30. CONCLUSION: These data support a role for both oxidative and nitrosative stress in rejection and the immunoregulatory potential of antioxidant therapy after transplantation.

Animals↗
PubMed2000

Glycosylation of phytepsin and expression of dad1, dad2 and ost1 during onset of cell death in germinating barley scutella.

Dysfunction and downregulation of dad (defending against death) has been linked to programmed cell death (PCD) in animals and plants. As DAD is an essential subunit of the oligosaccharyltransferase that is located in the ER membrane, the results have raised the possibility that downregulation of N-linked glycosylation could be involved in the regulation of PCD. Here we show that the 16 kDa subunit of phytepsin, a vacuolar proteinase, is normally processed and glycosylated at the onset of DNA fragmentation in germinating barley scutella. Two cDNA clones encoding dad (dad1, dad2), and one cDNA encoding another subunit of the same oligosaccharyltransferase complex (ost1) were isolated from barley. Northern analysis of germinating scutella show that the expression of only dad1 is declining before onset of DNA fragmentation. In contrast to this, the expression of both dad2 and ost1 increase before onset of DNA fragmentation.

Apoptosis Regulatory Proteins↗
PubMed2000

Experience in qualitative and quantitative FDG PET in follow-up of patients with suspected recurrence from head and neck cancer.

We evaluated positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in the detection of recurrent head and neck cancer, and compared visual and quantitative interpretation of PET images for their accuracy in the identification of tumour recurrence. Sixty-two FDG PET studies were performed in 56 patients having a total of 81 lesions, which were clinically suspected for recurrent carcinoma of the head and neck. The PET images were interpreted visually, and tracer uptake was quantitated as the standardised uptake value adjusted to body weight (SUV). Sensitivity of visual interpretation of the PET images for the presence of malignancy ranged from 84 to 95%, and specificity from 84 to 93%, respectively, depending on the selected scheme for grading of the lesions. Malignant lesions accumulated significantly more FDG than the benign ones (the median SUVs were 6.8 and 3.3, respectively, P<0.001). However, there was a wide overlap of the FDG uptake values between these two groups. Hence, the highest accuracy of quantitative analysis in correct identification of tumour recurrence (75% at Receiver Operating Curve analysis) was inferior to that of visual analysis (89%). FDG PET is feasible for the detection of recurrent head and neck cancer. Although quantitation of FDG uptake using SUV shows significantly higher tracer concentrations for malignant than benign lesions, the wide overlap of individual SUVs between these two groups is a serious concern in diagnostic evaluation. Therefore, in clinical practice it may be preferable to identify the presence of tumour recurrence within this patient group by qualitative interpretation of the PET images.

Adult↗
PubMed2000

Epidemiology of unintentional drowning and near-drowning in Denmark in 1995.

OBJECTIVES: To determine the pattern of accidental drowning and near-drowning in Denmark. DESIGN: Prospective study of all cases of accidental drowning and near-drowning during one year. SETTING: Denmark, 1995. SUBJECTS: All patients brought to Danish hospitals after incidents of unintentional near-drowning or cooling in water and all fatal cases. MAIN OUTCOME MEASURES: Number of near-drowned patients reported prospectively by hospital departments supplemented by cases reported after requests based on the National Patient Register. Number of drownings reported by public health medical officers (as medical examiners), institutes of forensic medicine, and hospitals. RESULTS: Sixty three (38%) of 167 unintentionally immersed persons died: eight (17%) of 47 children and 55 (46%) of 120 adults. The annual incidence of serious immersion events in children leading to hospital contact was 5.2/100,000; mortality was 0.7/100,000. For adult males the annual incidence of serious unintentional immersions was 4.3/100,000 and for females 1.2/100,000. For foreigners the risk was three to four times higher than for Danes. CONCLUSIONS: More attention should be paid to the risk of drowning in children, adult males, and foreigners.

Adolescent↗
PubMed2000

Nodal staging of lymphoma with whole-body PET: comparison of.

UNLABELLED: Accurate staging is elementary for optimal management of malignant lymphoma. Advanced cases may be curable with multidrug chemotherapy combined with radiotherapy, whereas limited disease can sometimes be cured by local radiotherapy only. Recently, FDG imaging with whole-body PET (WB PET) has been introduced as an accurate method for staging lymphoma. We evaluated the usefulness of L-[methyl-11C]methionine (MET) in comparison with FDG as a tracer for nodal staging of lymphoma with WB PET. METHODS: Nineteen patients with untreated, histologically proven malignant lymphoma underwent WB PET imaging with MET and FDG within 1 wk before treatment. Fourteen patients had non-Hodgkin's lymphoma (NHL), and 5 had Hodgkin's disease (HD). Two of these 19 patients were excluded from the final analysis because of hyperglycemia. WB PET images using FDG and MET were visually compared by 3 independent interpreters, and the PET findings were correlated with the data on the basis of conventional staging studies. RESULTS: Fifty-five of 178 lymph node regions were classified as diseased both by FDG PET and by CT, and 54 of 178 were classified as diseased both by MET PET and by CT. In addition, 11 lymph node regions that CT showed to be normal avidly accumulated FDG. Ten of these lymph node regions also had clear uptake of MET. Another 4 and 5 lymph node regions were enlarged at CT but were judged to be normal by FDG and MET PET, respectively. In nodal staging, both FDG PET and MET PET would have upstaged the disease in 3 patients. MET PET would also have downstaged the disease in 1 patient. CONCLUSION: FDG and MET seem to be comparable in the detection of lymphoma by WB PET. However, visual interpretation of the images tends to be hampered more by physiologic accumulations of MET than by normal accumulations of FDG, and MET may be preferable to FDG in hyperglycemic patients undergoing staging studies with PET.

Adult↗
PubMed1999

Clinical correlations of genetic changes by comparative genomic hybridization in Ewing sarcoma and related tumors.

Our previous comparative genomic hybridization (CGH) study of Ewing sarcoma and related tumors showed that DNA sequence copy number increases of 1q21-q22 and of chromosomes 8 and 12 were associated with trends toward poor survival (Armengol et al., Br J Cancer 1997, 75, 1403-1409). These trends were not statistically significant. In the present study, we analyzed 28 primary Ewing sarcomas and related tumors by CGH to study whether these (or other) changes have prognostic value in these tumors. Twenty-one tumors (75%) had changes with a mean of 1.9 changes per tumor. The most frequent aberration was gain of chromosome 8 in 10 tumors (36%). Five tumors (18%) had copy number increases at 1q21-22 and 5 had gain of 7q. Copy number increase of 6p21.1-pter, gain of chromosome 12, and loss of 16q were seen in 11%. Copy number increases of 1q21-q22 and of chromosomes 8 and 12 were associated with trends toward worse outcome, but the differences did not reach statistical significance. A novel finding is the association of copy number increase at 6p with worse distant disease-free (P = 0.04) and overall survival (P = 0.004). To confirm this finding and to see whether copy number increases of 1q21-q22 and of chromosomes 8 and 12 have definite prognostic value, a larger number of cases needs to be studied.

Adolescent↗
PubMed1999

Evaluation of early response to radiotherapy in head and neck cancer measured with [11C]methionine-positron emission tomography.

PURPOSE: To evaluate whether positron emission tomography (PET) with carbon-11-methionine (MET) can be used for detection of early response to external beam radiotherapy (RT) in untreated head and neck cancer using locoregional control and survival as study endpoints. MATERIALS: Fifteen patients with head and neck cancer underwent a MET PET study before RT and after a median dose of 24 Gy. Fractionation was standard (n = 6) or hyperfractionated (n = 9), and 13 out of 15 patients had planned surgery after RT. SUV was calculated for primary tumor (n = 13) or largest lymph node metastasis in two patients of whom one had his primary excised before study enrollment and one presented with unknown primary tumor syndrome. METHODS: Attenuation corrected PET scans acquired 20-40 min from tracer injection were used for evaluation of MET uptake in tumors. A quantitative MET uptake index was expressed as standardized uptake value (SUV) or SUV(lean) (corrected for lean body mass). The PET results were correlated with clinical follow-up data. The median follow-up time is currently 28 months (range 22-34). RESULTS: A total of 13 primary tumors and 12 metastatic lymph nodes were visually identified in MET PET. In the first PET study the median SUV in tumor was 8.6 (range, 5.5-14.0). In the second PET study performed during RT the median SUV decreased to 5.7 (range, 3.1-8.2, P = 0.001). Two out of 15 patients showed no radiation-induced decrease in SUV. The median tumor SUV ratio of patients remaining in local control (CR) after RT was 0.7 (range 0.6-0.8, n = 6), and that of relapsing patients similarly 0.7 (range 0.5-1.0, n = 9, NS). The SUV ratio was not associated with survival time. The MET uptake of submandibular salivary glands decreased in all patients during the first two or three weeks of RT (P = 0.03). CONCLUSIONS: MET uptake in tumor shows a significant decrease during the first two to three weeks of RT of head and neck cancer. It appears that the rate of decrease in tracer uptake is comparable in relapsing patients and those who remain locally controlled and thus the use of MET PET for prediction of response to RT is limited.

Aged↗