Single-shot mega-electronvolt ultrafast electron diffraction for structure dynamic studies of warm dense matter.

We have developed a single-shot mega-electronvolt ultrafast-electron-diffraction system to measure the structural dynamics of warm dense matter. The electron probe in this system is featured by a kinetic energy of 3.2 MeV and a total charge of 20 fC, with the FWHM pulse duration and spot size at sample of 350 fs and 120 µm respectively. We demonstrate its unique capability by visualizing the atomic structural changes of warm dense gold formed from a laser-excited 35-nm freestanding single-crystal gold foil. The temporal evolution of the Bragg peak intensity and of the liquid signal during solid-liquid phase transition are quantitatively determined. This experimental capability opens up an exciting opportunity to unravel the atomic dynamics of structural phase transitions in warm dense matter regime.

Accuracy of tele-oncology compared with face-to-face consultation in head and neck cancer case conferences.

Telemedicine was introduced for weekly tumour case conferences between Sahlgrenska University Hospital and two district hospitals in Sweden. The accuracy of tele-oncology was determined using simulated telemedicine consultations, in which all the material relating to each case was presented but without the patient in person. The people attending the conference were asked to determine the tumour ('TNM') classification and treatment. The patient was then presented in person, to give the audience the opportunity to ask questions and perform a physical examination. Then a new discussion regarding the tumour classification and the treatment plan took place, and the consensus was recorded. Of the 98 consecutive patients studied in this way, 80 could be evaluated by both techniques. Of these 80, 73 (91%) had the same classification and treatment plan in the telemedicine simulation as in the subsequent face-to-face consultation. In four cases the TNM classification was changed and for three patients the treatment plan was altered. The specialists also had to state their degree of confidence in the tele-oncology decisions. When they recorded uncertainty about their decision, it was generally because they wanted to palpate the tumour. In five of the seven patients with a different outcome, the clinical evaluation was stated to be dubious or not possible. The results show that telemedicine can be used safely for the management of head and neck cancers.

Laminin-5 as a predictor of invasiveness in cancer in situ lesions of the larynx.

Squamous epithelial cancer in situ (CIS) of the upper aerodigestive tract is a histopathologically well-defined condition. There is yet no reliable way to predict whether a CIS lesion will progress to invasive cancer, remain stable or regress. In the search for markers able to foretell clinical outcome, we performed immunohistochemical staining with a polyclonal antibody against recombinant gamma 2 chain of laminin-5 in 33 laryngeal CIS lesions. All six CIS lesions which progressed to invasive cancer, within a follow-up time of 5 years, were laminin-5 positive (100%), whereas only 10 out of 27 lesions which did not progress were positive (37%) (p < 0.01). Our data showed that a positive laminin-5 laryngeal CIS lesion indicates a high risk for progression to invasive cancer.

Overexpression of p53-related proteins predicts rapid growth rate of head and neck cancer.

OBJECTIVES/HYPOTHESIS: The p53 tumor suppressor gene plays an important role for cell cycle regulation and is the most frequent mutated gene in head and neck cancer. Controversy remains regarding the biological and clinical value of immunohistochemical identification of the proteins accumulated in association with inactivation of the p53 gene and increased tumor growth. Therefore, the objective of the present study was to perform a cell kinetic analysis of cases with untreated squamous cell carcinoma and to compare the result with immunostaining for p53-related proteins in the tumor cells. STUDY DESIGN: A prospective series of 32 patients presenting with various stages of untreated squamous cell carcinoma of the head and neck were included. Bromodeoxyuridine (BrdU) was injected as a tracer dose before tumor biopsy for cell kinetic analysis, and p53 protein accumulation was detected using two antibodies (DO7 and PAb 1801). RESULTS: Antibody DO7 showed the highest and the optimal immunoreactivity. Diploid tumors were found in 27 cases (84%), and the mean potential doubling time (Tpot) was 55 +/- 7 hours for these tumors. Positivity of DO7 (>1%) was demonstrated in 85% of the cases. However, a discrimination level exceeding 20% was required to obtain a significant negative relationship (Spearman's rank correlation coefficient test, P < or = .03) between Tpot and DO7 positivity. At that level, 33% of the tumors remained DO7-positive. The corresponding Tpot was not significantly different from the overall mean. The rates of metastatic disease and survival were not dependent on DO7 immunoreactivity or cancer cell kinetics. CONCLUSION: Accumulation of p53-related proteins is associated with an unrestrained growth of head and neck cancer.

The lack of correlation between proliferation (Ki-67, PCNA, LI, Tpot), p53 expression and radiosensitivity for head and neck cancers.

A study was made of the relationship between measurements of radiosensitivity versus proliferation and p53 status in head and neck cancers. Inherent tumour radiosensitivity was assessed as surviving fraction at 2 Gy (SF2) using a clonogenic soft agar assay (n = 77). The results were compared to data on proliferation obtained by both flow cytometry (labelling index (LI), the potential doubling time (Tpot) n = 55) and immunohistochemistry (Ki-67 and PCNA; n = 68), together with immunohistochemical p53 expression (n = 68). There were no overall significant differences in the median values of the various parameters analysed for the different sites within the head and neck region, disease stages, grades of tumour differentiation or nodal states. A subgroup analysis showed that oropharyngeal (n = 22) versus oral cavity (n = 35) tumours were more radiosensitive (P = 0.056) and had a higher Ki-67 index (P = 0.001). Node-positive tumours had higher LI (P = 0.021) and a trend towards lower Tpot (P = 0.067) values than node-negative ones. No correlations were seen between SF2 and any of the parameters studied. The long-standing dogma of an increased radiosensitivity of rapidly proliferating cells in contrast to slowly proliferating cells was not confirmed. The study shows that parallel measurements of different biological markers can be obtained for a large number of patients with head and neck cancers. The independence of the various parameters studied suggests that there may be potential for their combined use as prognostic factors for the outcome of radiotherapy.

Malnutrition and food intake in relation to quality of life in head and neck cancer patients.

BACKGROUND: The quality of life (QL) of cancer patients has attracted an increasing interest in recent years. Patients with head and neck cancer often have troublesome symptoms due to the disease and to treatment side effects, which will have an impact on the patient's QL. The aim of this study was to evaluate the possibility of studying QL in relation to well-known clinical parameters. METHODS: Patient's QL was evaluated according to the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) combined with a diagnosis-specific questionnaire. Quality of life was measured in a cross section of head and neck cancer patients (n = 48) and related to nutritional status, energy intake, severity of disease, and 2-year survival. RESULTS: Fifty-one percent of the patients (mean age, 67 years) fulfilled the criteria proposed for malnutrition, and 55% had a negative energy balance. We did not find any correlation between the severity of the cancer disease and the patient's self-rated QL. However, we found significantly better QL ratings among the 2-year survivors (mean, 63; range 52-76 versus mean, 42; range, 31-54; p < .05). There were few correlations between the QL items and malnutrition. CONCLUSIONS: Quality of life measurements offer objective information on well-being, sometimes quite opposite that of other clinical parameters, such as tumor stage. Furthermore, QL measurements may be of prognostic value concerning the survival of head and neck cancer patients.

Tumor necrosis factor-alpha response and herpesvirus infection in Bell's palsy.

OBJECTIVES: To attempt early diagnosis of patients with Bell's palsy by detection of herpesviral DNA in body fluids, and to investigate whether tumor necrosis factor-alpha (TNF-alpha), a cytokine associated with demyelination, is involved in the inflammatory response in this disease. STUDY DESIGN: Eleven patients with acute facial palsy admitted within 1 week after onset of the disease were followed in a consecutive prospective study. METHODS: Antibodies reactive to herpesviruses were determined by enzyme-linked immunosorbent assay in serum samples from acute and convalescent (> 2-week interval) cases. Intrathecal antibody response was investigated by immunoblotting. Polymerase chain reaction amplification of herpesviral DNA was attempted from samples of serum, cerebrospinal fluid, tear fluid, and saliva TNF-alpha and its soluble receptors (types I and II) were assessed in serum and cerebrospinal fluid samples. RESULTS: Ten of the 11 patients demonstrated serologic evidence of herpesviral primary infection or reactivation, supporting the evidence that herpesviruses are the most prevalent etiologic agents in Bell's palsy. Despite this, DNA amplifications by polymerase chain reaction were negative for herpesviruses in the body fluids tested. TNF-alpha concentrations were significantly elevated in serum, as compared with controls. Only one patient had a remaining facial nerve dysfunction at follow-up after 3 months. CONCLUSION: The absence of herpes DNA in body fluids in the acute stage of serologically confirmed Bell's palsy suggests that viral replication is transient in cases with an early restoration of the facial nerve function. The elevated serum levels of TNF-alpha indicate that this cytokine might be a pathogenetic factor related to the demyelination in this disease.

Tumor suppressive action of indomethacin is NK-cell-independent.

This study was undertaken to determine whether NK-cells constitute a necessary mediator for the suppression of tumor growth by indomethacin. C57Bl mice with a methylcholantrene (MCG 101) tumor were studied. Indomethacin treatment was provided by daily subcutaneous injections (1 microgram/g body weight). NK-cells were depleted by treatment with a monoclonal antibody to NK1.1. Consecutive indomethacin injections prolonged survival in tumor bearing animals. Indomethacin was equally effective in animals with intact NK-cells as in NK-cell-depleted animals. Further, the MCG cells were apparently insensitive to the lytic activity of NK-cells in vivo. Thus, the clearance of intravenously injected MCG cells from lungs was not affected by depletion of NK-cells in vivo; in contrast, the corresponding clearance of NK-cell-sensitive YAC-1 lymphoma cells was strikingly reduced by the depletion of NK-cells. Our data suggest that NK cells are not a necessary mediator for the suppression of tumor growth by indomethacin.

Percutaneous sclerotherapy of venous malformations of the head and neck using sodium tetradecyl sulphate (sotradecol).

Thirty-eight patients with venous malformations of the face, neck, and tongue underwent percutaneous sclerotherapy with direct puncture and instillation of sodium tetradecyl sulphate (Sotradecol) (33-67% solution, mixed with contrast material) into the lesions. Each patient underwent from one to seven treatment sessions (mean 2.2), followed by reconstructive surgery in three cases. Of the 34 patients who responded to the follow-up questionnaire, the late results were excellent or good in 23 patients (68%), moderate in eight, unchanged in three, and were worse in one. Compared with our previous experience of embolisation of such malformations with ethanol, the results with Sotradecol were slightly worse. There was one serious complication, unilateral loss of vision in a patient with a large malformation that extended to the orbit. In conclusion, percutaneous sclerotherapy with Sotradecol is effective treatment for venous malformations of the head and neck. Careful planning is essential to reduce the risks of the treatment.

Cell proliferative modulation of MCG 101 sarcoma from mice exposed to hyperbaric oxygenation.

Tumor cell kinetics were studied in C57 Bl/J mice with a transplantable sarcoma, MCG 101, exposed to hyperbaric oxygen (HBO2), 2.8 atm abs, 2 hours daily for 9 days or until spontaneous death. The isoenzymatic pattern of lactate dehydrogenase (LDH) confirmed that there was a significant shift toward aerobic metabolism in tumor tissue as well as in the liver and skeletal muscle. Recruitment of cells from the G0G1 state into DNA synthesis was associated with an increased mobilization of substrates for polyamine synthesis in terms of an elevated ornithine decarboxylase (ODC) activity. However, cell cycle turnover in terms of bivariate flow cytometric analysis after bromodeoxyuridine (BrdUrd) injection, final tumor weight, and survival time were not changed compared with the controls. Tumor cell metabolism demonstrated evidence of an unchanged net energy utilization, in that activities (V(max) of phosphofructokinase (PFK) and LDH were not significantly changed. When the tumor-bearing animals were exposed to advanced HBO2 pressure (3.7 atm abs) for 3 h as a single dose, the DNA distribution and growth rate were not changed immediately. However, 3.5 h later we observed a DNA pattern similar to that after repeated HBO2 treatments, 2.8 atm abs, concomitant with a preponderance of cells in the late S-phase, which is consistent with a block at the entry of G2M. We conclude that MCG 101 sarcoma recovers from HBO2 exposure by an accumulation of cells in the S-phase without significant changes of net tumor growth. This may have relevance to clinical radiocurability.

Tumour purine nucleotides and cell proliferation in response to exercise in rats.

Voluntary physical exercise can delay the onset of anorexia and cachexia in tumour-bearing rats. A substrate deviation in the host which has been hypothesised as tumour burden is reduced despite an increase in food intake. Therefore, we determined the levels of purine nucleotides, the energy charge and the cell division rate in tumours from exercising animals in the postexercise period. Tumour content of purine nucleotides was analysed by HPLC. Tumour cell kinetics was studied by flow cytometry after incorporation of bromodeoxyuridine (BrdU) into DNA. Exercising animals demonstrated a 34.4% reduction in tumour volume (P < 0.05) but a 1.31-fold increase in energy charge in tumour tissue (P < 0.05). Labelling index (LI), DNA synthesis time (Ts) and potential doubling time (Tpot) were not significantly altered. These results suggest that the influence on tumour growth is closely related to the exercise period.

Effects of nandrolone propionate on experimental tumor growth and cancer cachexia.

We studied the tumor host response to excessive doses of an anabolic steroid (nandrolone propionate, 2.5 mg 20 g intraperitoneally every second day for 11 days) with respect to body composition and tumor cell kinetics in MCG 101 sarcoma-bearing mice (C57BL/6J) with progressive cachexia. Although survival and food intake were not affected, a significant weight gain was observed that was essentially attributed to water retention. Net protein content was increased only to a minor extent (15%), of which only the liver accounted for a significant part of the body compartments. Hepatic protein accumulation was obviously caused by decreased protein degradation, since hepatic RNA content was unchanged. After anabolic steroid administration, reduced histochemical staining of succinate dehydrogenase was observed in skeletal muscles rich in oxidative type 1 fibers, but it was not different from that of tumor-bearing control animals, which was also confirmed by measurements of citrate synthase and cytochrome c oxidase activities in skeletal muscle and liver tissue. The anabolic steroid had no significant effect on tumor growth in terms of weight progression, energy state, polyamine synthesis rate, cell division rate, and cell cycle cytocompartments. We conclude that anabolic steroid supplementation is not therapeutically beneficial in counteracting progressive weight loss in experimental cancer.

Renal biopsy in children: indications, technique and efficacy in 119 consecutive cases.

Consecutive renal biopsies were performed on native kidneys in 109 children and adolescents, aged 0.1-19.8 (mean 9.9) years (119 biopsies). Bleeding diatheses were excluded or treated pre-operatively with intravenous desmopressin acetate. Biopsies were performed by a radiologist under ultrasound imaging, using an automated spring-loaded device allowing selection of the length of the needle movement and score size. Diagnostically adequate tissue was retrieved in 118 of 119 (99.2%) biopsy procedures; 24-h post-biopsy ultrasonography disclosed a small haematoma of the biopsied kidney in 26% of the cases. No correlation was seen between the occurrence of haematoma and (treated) prolonged bleeding time or a decrease in the haemoglobin level. No major complications occurred. Newly developed macroscopic haematuria was reported by 7% and micturition pain by 7% of patients. Painful body movements were reported by 37%. We conclude that the use of ultrasound imaging and an automated gunshot technique is a safe and efficient method for performing renal biopsies in paediatric patients.

Effects related to indomethacin prolonged survival and decreased tumor-growth in a mouse-tumor model with cytokine dependent cancer cachexia.

Tumor-bearing mice with two different locally growing malignant tumors (epithelial like, MCG 101; malignant melanoma, K1735-M2) were used to evaluate the putative role of prostaglandins for survival and local tumor growth in experimental cancer. Daily systemic injections of indomethacin (1 mu g/g bw) were used to block prostaglandin production in normal and T-cell deficient tumor-bearing nude mice. Tumor progression was determined by measurements of tumor weight, DNA-synthesis, cell cycle kinetics in vivo and in vitro (flow cytometry), tumor tissue concentrations of polyamines (putrescine, spermidine, spermine) and tumor tissue gene expression of growth regulating factors (IL-1 alpha, IL-6, TNF alpha, A,B-PDGF, EGF, VEGF, bFGF, TGF beta(3), angiogenin and transferrin receptor). Tumor tissue content of von Willebrandt factor VIII was estimated by immunohistochemistry. Indomethacin had no effect on survival, host nutritional state or local tumor growth in mice bearing the malignant melanoma with low PGE(2) production. In contrast, indomethacin prolonged survival, improved cachexia and decreased tumor growth in mice bearing the MCG 101 tumor with hundredfold higher prostaglandin tumor production, leading to elevated liver and muscle tissue as well as plasma concentrations of PGE(2). Indomethacin inhibited almost completely the high tumor PGE(2) production in MCG tumors, leading to prolonged potential doubling time for tumor growth in vivo, and a trend to decreased tumor tissue concentration of polyamines (spermidine). Indomethacin had no inhibitory effect on tumor cell proliferation in vitro, although PGE(2) production was decreased by 75%. The effect of indomethacin in vivo was independent of T-cells and was observed with similar magnitude irrespective of the number of MCG cells (10(4)-10(6)) implanted or the site of implantation (s.c., i.p., liver, lung, skeletal muscles). Tumor growth inhibition by indomethacin was not intrinsically transferable by tumor cells from indomethacin treated tumor-animals. Tumor expression of mRNA for several growth regulating factors were either increased (IL-6, TNF alpha, GM-CSF, TGF beta(3)) unchanged (EGF, VEGF, PDGF A,B, IL-1 alpha, transferrin receptor) or decreased (b-FGF and angiogenin) (p<0.05) by indomethacin treatment of MCG mice. Decreased tumor content of von Willebrandt factor VIII in combination with an attenuated tumor vasculature were associated with decreased tumor growth (p<0.05). Our results confirm that high tumor production of prostaglandins was related to reduced survival. Tumor prostaglandins probably promote local tumor growth by stimulation of tumor surrounding cells to produce growth factor(s) for tumor angiogenesis including tumor and matrix cell proliferation unrelated to immune cells.

Elective lymph node dissection in stage I cutaneous malignant melanoma of the head and neck. A report from the Swedish Melanoma Study Group.

The effect of elective lymph node dissection in patients with cutaneous malignant melanoma of the head and neck was investigated in a retrospective study. Of 517 patients in clinical stage I, 84 underwent elective dissection of the ipsilateral neck lymph nodes. In six of these patients, lymph node metastases were demonstrated at histopathological examination. There was a slight reduction in the incidence of recurrent disease in the regional lymph nodes in the group of patients who had undergone elective lymph node dissection, but this difference was not statistically significant. No significant differences were seen between the two groups regarding overall survival of disease-related survival.

Sudden sensorineural hearing loss and hemostatic mechanisms.

OBJECTIVE: To evaluate the possible causal role of pathologic hemostatic mechanisms in sudden hearing loss. DESIGN: The study was prospective. SETTING: The patients were hospitalized, and all tests were performed at the hospital. PATIENTS: Thirty-two consecutive patients with sudden hearing loss participated, as well as a control group of 28 healthy individuals. The control group was matched with regard to body mass index. MAIN OUTCOME MEASURES: Venous blood analyses were made regarding general blood parameters, as well as specific hemostatic parameters. RESULTS: Twenty-five of the patients had some kind of aberration of specific hemostasis parameters; seven patients had an increase in the activity of the plasminogen activator inhibitor 1 (ie, a glycoprotein associated with diminished fibrinolysis) compared with that in the control group (P < .05). Increased plasminogen activator inhibitor levels were most frequently observed among the patients who were overweight. Seven of the oldest patients had an increase of D-dimers, ie, a degradation product of fibrin, and most of these patients had a history of cardiovascular disease. CONCLUSION: Although isolated aberrations in the hemostatic pathway were observed, we concluded that pathologic hemostasis does not seem to have a decisive importance for the pathogenesis of sudden deafness.

Nuclear DNA content, proliferating-cell nuclear antigen (PCNA) and p53 immunostaining in predicting progression of laryngeal cancer in situ lesions.

Squamous epithelial cancer in situ (CIS) of the upper aerodigastric tract is a histopathologically well-defined condition. However, in clinical practice, morphological grading of dysplasia is difficult and shows large variability. The biology of CIS remains enigmatic, and there is yet no reliable way to predict whether a CIS lesion will progress to invasive cancer, remain stable or regress. In the search for markers able to foretell clinical outcome, we performed image DNA cytometry (ICM) and immunohistochemical staining for PCNA as well as p53 in 38 laryngeal CIS lesions, of which 9 progressed to invasive cancer. The majority of the CIS lesions displayed high-grade DNA aberration, a high PCNA-positive rate, and every third lesion was p53-positive by immunostaining. The lesions which progressed to invasive cancer showed a clear tendency towards more pronounced DNA aberration, a higher percentage of intense PCNA staining and more frequent p53 positivity. By combining the results from the analyses of DNA, PCNA and p53 in a prognostic index for each individual case, we correctly classified 82% of the lesions as progressors or non-progressors.

Peripheral facial palsy: antibody levels to Borrelia in serum and CSF.

Serum antibodies to Borrelia burgdorferi antigen were determined in 71 consecutive patients with an acute peripheral facial palsy. The study was conducted for one year in a south western coastal region in Sweden. Twenty-one per cent of the patients had significantly elevated serum levels of antibodies to Borrelia burgdorferi antigen. CSF was examined in 13 of the sero-positive patients. In three of these (23%) Borrelia antibodies were found. Another five patients had a pathological protein and cell pattern in the CSF. No seasonal differences were observed. Four of the sero-positive patients had a long-term history of dermatological neurological manifestations compatible with the late third stage of the disease.

Energetics of nutrition and polyamine-related tumor growth alterations in experimental cancer.

The aim of this study was to evaluate whether food intake modulates experimental tumour growth by acute alterations in the energy state and blood flow of the tumour, and if so whether such changes are related to alterations in the enzyme ornithinedecarboxylase (ODC) and DNA synthesis. Inbred mice (C57BL/J) bearing a syngeneic undifferentiated and rapidly growing tumour were used. The tumour levels of high energy phosphates were measured in vivo by 31-P-NMR spectroscopy and biochemically following tissue extraction. DNA synthesis was estimated by measuring the incorporation of bromodeoxy-uridine into tumour DNA. Difluoro-methylornithine (DFMO) was used to inhibit ODC-activity. Tumour blood flow was estimated by a 132Xe local clearance technique. Tumour progression was associated with a significant decrease in tumour tissue high energy phosphates. Acute starvation decreased DNA-synthesis and tumour energy charge as well as its PCr/Pi which were rapidly normalised during subsequent refeeding. These changes were related to similar alterations in tumour blood flow. The inorganic phosphate (Pi) resonance and the resonances in the phosphomonoester (PME) region were considerably increased in tumour tissue. Inhibition of ODC-activity by DFMO decreased DNA-synthesis, which was associated with a secondary increase in tumour high energy phosphates probably due to a lowered energy demand for tumour cell division. The results demonstrate that host undernutrition was translated into retarded tumour growth associated with a decrease in the energy state and blood flow of the tumour. The results have bearing for the evaluation and planning of all treatment protocols with potential influence on food intake in experimental tumour-bearing animals.