In young patients with stroke of undetermined etiology, large vessel occlusions are less frequent in the group with high-risk patent foramen ovale.

INTRODUCTION: Patent foramen ovale (PFO) is present in a significant proportion of young patients with stroke of undetermined etiology, but is not always causal. Therefore, classifications (RoPE, PASCAL) have been developed to determine the probability that PFO is the stroke cause. However, the presence of an initial arterial occlusion as a prediction factor was not studied when these classifications were built. Our aim was to evaluate the presence of arterial occlusion in young patients with stroke of undetermined etiology with/without high-risk PFO. METHODS: From a prospectively-built monocentric database, we identified patients aged≥18 to<60-years with strokes of undetermined etiology and complete etiological work-up, including transesophageal echocardiography. We divided patients in two groups: (i) with high-risk PFO [i.e. PFO with large interatrial shunt (>30 microbubbles) or associated with atrial septal aneurysm] and (ii) with low-risk/without PFO. We recorded the presence of arterial occlusion and large vessel occlusion (LVO) in the acute phase. RESULTS: We included 96 patients; 55 (57%) had high-risk PFO. Their median age was 48 (40-52) years, and 28 (29%) were women. The percentages of patients with arterial occlusion and with LVO were lower in the high-risk PFO group than in the low-risk/without PFO group: 11 (20%) versus 19 (46%) (P=0.008), and 5 (9%) versus 15 (37%) (P=0.002), respectively. There was no difference in the median RoPE score between groups (P=0.30). CONCLUSION: The presence of LVO could represent a "red flag" of PFO causality in stroke of undetermined etiology, and could be implemented in future PFO-related stroke classifications.

Clinical and serological predictors of relapse in pemphigus: a study of 143 patients.

BACKGROUND: Pemphigus is an autoimmune bullous disease mediated by autoantibodies targeting epithelial cell-cell adhesion molecules. Predictors of relapse have not yet been clearly identified. AIMS: To identify factors at diagnosis and during follow-up that could be predictors of relapse. METHODS: Clinical and immunopathological data at diagnosis, clinical remission and first relapse from patients with pemphigus vulgaris or foliaceus and at least a 36-month follow-up were collected retrospectively. Based on the autoantibody profile at diagnosis, three serological patient subsets were devised: (i) anti-desmoglein (Dsg)1-positive and anti-Dsg3-negative; (iii) anti-Dsg1-negative and anti-Dsg3-positive; and (iii) anti-Dsg1-positive and anti-Dsg3-positive. RESULTS: Data from 143 patients were collected. No significant differences were found between relapsers (n = 90) and nonrelapsers (n = 53) for time to remission or for anti-Dsg1 and anti-Dsg3 titres at diagnosis and remission. In the analysis of all patients, a higher risk of relapse was found for a body surface area (BSA) score of 3 compared with BSA < 3 (OR = 3.30, 95% CI 1.17-9.28; P = 0.02) and for a positive titre of either anti-Dsg1 or anti-Dsg3 autoantibodies at remission compared with both being negative (OR = 2.42, 95% CI 1.21-4.85, P = 0.01). In patients who were anti-Dsg3-positive and anti-Dsg1-negative at diagnosis, failure to achieve anti-Dsg3 negativity at clinical remission was a significant predictor of relapse (OR = 7.89, 95% CI 2.06-30.21; P < 0.01). Similarly, failure to achieve anti-Dsg1 negativity at clinical remission was a significant predictor of relapse in patients with both anti-Dsg1 and anti-Dsg3 positivity at diagnosis (OR = 5.74, 95% CI 1.15-28.61; P = 0.03), but not in those who were anti-Dsg1-positive/anti-Dsg3-negative at diagnosis (OR = 1.08, 95% CI 0.27-4.30; P = 0.91). CONCLUSION: Regardless of pemphigus subtype, autoantibody titre negativity at clinical remission in patients classified based on their anti-Dsg1 and anti-Dsg3 profile at diagnosis and BSA were useful tools in predicting relapse.

A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

A regional strategy to decrease the time to thrombectomy in patients with low probability of treatment by thrombolysis.

BACKGROUND AND PURPOSE: The best transportation strategy for patients with suspected large vessel occlusion (LVO) is unknown. Here, we evaluated a new regional strategy of direct transportation to a Comprehensive Stroke Center (CSC) for patients with suspected LVO and low probability of receiving intravenous thrombolysis (IVT) at the nearest Primary Stroke Center (PSC). METHODS: Patients could be directly transported to the CSC (bypass group) if they met our pre-hospital bypass criteria: high LVO probability (i.e., severe hemiplegia) with low IVT probability (contraindications) and/or travel time difference between CSC and PSC<15 minutes. The other patients were transported to the PSC according to a "drip-and-ship" strategy. Treatment time metrics were compared in patients with pre-hospital bypass criteria and confirmed LVO in the bypass and drip-and-ship groups. RESULTS: In the bypass group (n=79), 54/79 (68.3%) patients met the bypass criteria and 29 (36.7%) had confirmed LVO. The positive predictive value of the hemiplegia criterion for LVO detection was 0.49. In the drip-and-ship group (n=457), 92/457 (20.1%) patients with confirmed LVO met our bypass criteria. Among the 121 patients with bypass criteria and confirmed LVO, direct routing decreased the time between symptom discovery and groin puncture by 55 minutes compared with the drip-and-ship strategy (325 vs. 229 minutes, P<0.001), without significantly increasing the time to IVT (P=0.19). CONCLUSIONS: Our regional strategy led to the correct identification of LVO and a significant decrease of the time to mechanical thrombectomy, without increasing the time to IVT, and could be easily implemented in other territories.

Prevalence of carotid web in a French cohort of cryptogenic stroke.

BACKGROUND AND PURPOSE: Carotid webs (CaW) may be an under-recognized cause of anterior circulation cryptogenic ischemic stroke (ACIS). Prevalence is still unknown in European patients with ACIS. OBJECTIVE: To evaluate the prevalence of CaW in ACIS and describe patients with CaW phenotype in a cohort of patients from a French stroke center. METHODS: We conducted a retrospective monocentric cohort study from 01/01/2015 to 31/12/2019 (Montpellier University Hospital, France), in consecutive anterior ischemic stroke (AIS) patients ≤65 years old from a prospective stroke database. Using ASCOD phenotyping, ACIS patients were selected and cervical CTA were reviewed to find CaW. RESULTS: Among 1053 consecutive AIS patients, 266 ACIS patients with CTA were included. Among patients included (mean age 50, women 58%), CaW was in the ipsilateral carotid (iCaW) in 21 patients: 7.9% (95%CI [4.6-11.1]), (mean age 51, 11 women, 16 Caucasian). iCaW were uncovered during study review of CTA in 6/21 (29%) patients. Comparison between patients with iCaW and those without iCaW showed no differences except that of a higher rate of intracranial large vessel occlusion (LVO) (62.4 vs 37.6%; p = 0.03). Patients with iCaW under conservative medical therapy had an annualized stroke recurrence rate (SRR) of 11.4% (95%CI [8.4-15.1]. CONCLUSIONS: iCaW was identified as a source of stroke in about 8% of a French population ≤65 years with ACIS. iCaW was associated with a higher rate of LVO and a high SRR under conservative medical therapy.

Identification of the hydration state in emergency patients: correlation between caval index and BUN/creatinine ratio.

BACKGROUND: Dehydration is a frequent clinical problem. No single laboratory value has been found to be accurate; however, the BUN/Creatinine Ratio appears the most sensitive parameter. The respiratory variation (Caval Index, CIn) in the diameter of the inferior vena cava has been investigated as a non-invasive marker for the intravascular volume status. AIM: The present study is performed with the aim to explore the relationship between CIn and BUN/creatinine ratio. PATIENTS AND METHODS: This prospective, observational study was conducted at Emergency Department (ED) of San Paolo Hospital (Savona, Italy), in October 2011. RESULTS: 113 patients were considered eligible (mean age of 63 years). We found a good correlation between CIn and BUN/Cr Ratio (Pearson Index 0.76, p < 0.001). Receiver operator characteristic curve (ROC) analyses indicated that the maximum value was 0.884 (p < 0.0001) and corresponded to CIn 60.7%, (sensitivity 79%, specificity 89%). CIn was a good predictor for patients with BUN/Cr ratio greater than 20, and was particularly strong in determining patients with lower BUN/Cr ratio. DISCUSSION: Our study suggests that inferior vena cava could provide indications on the state of hydration of the patients: we found that a caval index greater than or equal to 60% was associated with a BUN/Cr Ratio over 20, which is considered an important marker for dehydration. Therefore, bedside sonography can give emergency physicians immediate information on patient volume status long before obtaining laboratory findings. CONCLUSIONS: Our study seems to support the hypothesis that CIn can be a useful bedside marker to predict dehydration in Emergency Department (ED) patients.

Rare presentation of endometrial carcinoma with singular bone metastasis.

The major symptom at diagnosis of endometrial cancer is post-menopausal bleeding; it is present in around 90% of cases. Singular bone metastasis is described as an uncommon site for endometrial cancer at diagnosis, showing in just 5-6% of cases. In this report we describe a rare presentation of a singular bone metastasis because of endometrial cancer of a woman with previous diagnosis of early breast cancer. A review of literature uncovered some cases of bone metastasis at presentation of endometrial cancer and that it can occur as first symptom of cancer before vaginal bleeding. This rare presentation of uterine cancer needs to be studied and described because it may be seen and needs a homogeneous treatment to improve survival.

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer.

This study was performed to assess the efficacy and safety of docetaxel, cisplatin and fluorouracil combination in patients with unresectable locally advanced oesophageal squamous cell carcinoma. Treatment consisted of docetaxel 60 mg m(-2), cisplatin 75 mg m(-2) on day 1 and fluorouracil 750 mg m(-2) day(-1) on days 2-5, repeated every 3 weeks for three cycles, followed by carboplatin 100 mg m(-2) week(-1) for 5 weeks and concurrent radiotherapy (45 Gy in 25 fractions, 5 days week(-1)). After radiotherapy, eligible patients either underwent an oesophagectomy or received high dose rate endoluminal brachytherapy (HDR-EBT). Thirty-one out of 37 enrolled patients completed the planned chemotherapy and 30 completed chemoradiation. After completion of chemotherapy, 49% (95% CI: 32.2-66.2) had a clinical response. Twelve patients (32%) underwent a resection, which was radical in 60% (postoperative mortality: 0%). A pathological complete response was documented in four patients (11% of enrolled, 30% of resected). The median survival was 10.8 months (95% CI: 8.1-12.4), and the 1- and 2-year survival rates were 35.1 and 18.9%, respectively. Grade 3-4 toxicities were neutropoenia 32%, anaemia 11%, non-neutropoenic infections 18%, diarrhoea 6% and oesophagitis 5%. Nine patients (24%) developed a tracheo-oesophageal fistula during treatment. Even if the addition of docetaxel to cisplatin and 5-fluorouracil (5-FU) seems to be more active than the cisplatin and 5-FU combination, an incremental improvement in survival is not seen, and the toxicity observed in this study population is of concern. In order to improve the prognosis of these patients, new drugs, combinations and strategies with a better therapeutic index need to be identified.

Multimodal imaging of esophagus and cardia cancer before and after treatment.

PURPOSE: Prognosis and treatment of esophagus and cardia cancer (ECC) depend on the precision with which the disease is staged according to the American Joint Committee of Cancer (AJCC) criteria. Imaging modalities normally used in clinical staging are esophagography, esophagoscopy, endoscopic ultrasound (EUS), computed tomography (CT) and positron emission tomography- CT fusion (CT-PET). The combination of these methods is crucial in determining not only the right diagnosis but also the stage and follow-up after multimodal treatment. The purpose of our investigation was to define the role of each imaging modality in determining the most appropriate treatment options in patients with ECC. MATERIALS AND METHODS: Fifty-six patients with ECC diagnosed by X-ray of the upper digestive tract, endoscopy and biopsy were staged using EUS, chest and abdomen CT scan, and CT-PET. Thirty-four patients in stage II and 18 patients in stage III underwent surgery after neoadjuvant chemotherapy; four patients in stage IV were treated with the positioning of an endoprosthesis after chemoradiotherapy. In the 52 patients who had surgery, follow-up included digestive tract X-ray, endoscopy and CT of the chest and abdomen every 6-8 months for the first 3 years. CT-PET was only performed in patients with a clinical suspicion of recurrence and/or CT findings suspicious of persistent disease (12 cases). RESULTS: In all 56 patients, endoscopy, EUS, CT and CT-PET in combination were crucial in determining the site of disease, locoregional extent and depth of esophageal wall penetration (T), and any involvement of the mediastinal lymph nodes (N1), extrathoracic lymph nodes (M1) or hepatic metastases. In the locoregional staging of ECC before chemotherapy, we were able to differentiate T2-T3 from T4 in 40 patients; T4 disease was found in 12 potentially resectable cases. We were able to distinguish N0 from N1 in 12 patients. In four cases, the presence of small lymph node and/or liver metastases prompted positioning of an endoprosthesis. The specificity of CT in detecting small lymph nodes in the mediastinum was less than 50% while for CT-PET, it was more than 80%; EUS revealed sensitivity higher than 90% but a low specificity in seven cases. Only CT-PET revealed metastatic subdiaphragmatic lymph nodes (diameter <15 mm) in three cases. Presurgical restaging of the 18 patients (stage III) who had chemotherapy was based on endoscopy, EUS, CT of the chest and abdomen and CT-PET (only in suspected cases) and was compatible with surgery. Anastomotic recurrence was diagnosed in 16 patients by endoscopy with associated biopsy; any intramediastinal spread from anastomotic recurrences was evaluated by chest CT, and CT-PET in suspected cases. CONCLUSIONS: X-ray of the upper digestive tract and chest and abdomen CT scan are useful in preliminary evaluation of ECC. Endoscopy is particularly indicated for evaluating tumour morphology, taking biopsies for a histological diagnosis and the early diagnosis of anastomotic recurrences. EUS is indicated mainly for evaluating T stage before and after chemotherapy or chemoradiotherapy. CT-PET is extremely useful in identifying small mediastinal metastatic lymph nodes (N1) or extrathoracic lymph nodes (M1) and hepatic metastases (

Submersed culture production of extracellular wax esters by the marine bacterium Fundibacter jadensis.

Fundibacter jadensis strain T9, a marine gram-negative bacterium, was isolated from the intertidal sediment of the German North Sea coast by our group. The cells were able to produce considerable amounts of extracellular wax esters when cultivated with n-alkanes (hexadecane or tetradecane) as a carbon source. The dependence of wax ester production and the composition of the purified wax on different culture conditions (C:N:P ratio and dissolved oxygen tension) were tested. Our results show that wax ester production was not directly growth-linked. The C:N:P ratio had no significant influence on the yield of alkane-free purified wax. The dissolved oxygen tension affected the produced amount of the alkane-free purified wax and the composition of the purified wax; when lower than 2% it decreased the yield of purified wax and led to an altered wax ester composition. Tetradecane as a carbon source enhanced the spectrum of the wax ester composition.

Photofrin as a specific radiosensitizing agent for tumors: studies in comparison to other porphyrins, in an experimental in vivo model.

The use of ionizing radiation for tumor treatment represents a well established therapeutic modality. The efficiency and selectivity of radiotherapeutic protocols can be often enhanced by the addition of specific chemical compounds that optimise the response of the tumor to the incident radiation as compared with peritumoral tissue districts. The results of this study showed that Photofrin, a porphyrin derivative which is presently used as a tumor-photosensitizing agent in photodynamic therapy (PDT), can also act as an efficient tumor radiosensitizer. To test this possibility, we used nude mice subcutaneously implanted with human bladder cancer RT4. The mice were injected with different porphyrin-type photosensitizing agents, including Photofrin, 5-aminolevulinic acid, chlorin e(6), haematoporphyrin, protoporphyrin, Zn-tetrasulphophtalocyanine, and irradiated with 5 and 15 Gy using a Siemens X-ray device. Even though all the porphyrins accumulated in significant amounts in the neoplastic lesion, only Photofrin significantly improved the response of the tumor to irradiation by increasing the doubling time of the tumor volume from 6.2 days in the untreated control group to 10.9 days in the 5 and 15 Gy-irradiated groups. The tumor response was maximal with injected Photofrin doses of 7.5 mg/kg, and was not further enhanced by injection of higher doses. Our hypothesis is, that the radiosensitizing effect of Photofrin seems to be due to some oligomeric constituents which could specifically react with radiogenerated-radicals thereby amplifying the effect of the X-ray radiation.

Photofrin II as an efficient radiosensitizing agent in an experimental tumor.

BACKGROUND AND OBJECTIVE: The use of ionizing irradiation as radiation therapy (RT) for tumor treatment represents a well-established method. The use of photodynamic therapy (PDT), especially with Photofrin II, for tumor treatment is also known. Chemical modifiers enhancing the action of radiation therapy are well known and widely used in medicine. None of these compounds, however, is a selective radiosensitizer. MATERIALS AND METHODS: Several series of animal experiments were performed. The highly differentiated human bladder cancer cell line RT4 was implanted subcutaneously in nude mice. The mice were injected 10 mg/kg Photofrin II and irradiated with 5 Gy. RESULTS: Photofrin II has proved to be a chemical modifier of ionizing irradiation, enhancing the tumor doubling time (tumor growth) from 6.2 to 10.9 days in the control group with the use of irradiation and injection of porphyrin. CONCLUSION: Photofrin II shows a high activity as radiosensitizer and, in the future, can be used as a selective radiosensitizer for tumor treatment with ionizing radiation.

Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients.

This randomized phase II trial was performed to define the activity and toxicity of the combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP) and tamoxifen (DBDT regimen) versus DTIC alone in patients with metastatic melanoma. Sixty patients with metastatic melanoma were randomly assigned to receive BCNU 150 mg/m2 intravenously (i.v.) on day 1, cisplatin 25 mg/m2 i.v. daily on days 1 to 3, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and tamoxifen 160 mg orally daily for 7 days prior to chemotherapy (DBDT arm; arm A). Treatment cycles were repeated every 28 days, while BCNU was given every two cycles. The DTIC arm (arm B) patients received DTIC alone 1200 mg/m2 i.v. on day 1, repeated every 21 days. Patients were evaluated every two cycles; responding patients continued the treatment for a maximum of 12 cycles. The overall response rate was 26% in the DBDT arm and 5% in the DTIC arm. Complete responses were 2.5% for DBDT and 0% for DTIC. The median progression-free survival and the median survival were 4 and 9 months, respectively for DBDT, and 2 and 7 months for DTIC. DBDT was associated with significant haematological toxicity: 33% of the patients experienced a grade III or IV neutropenia and 28% a grade III or IV thrombocytopenia. In conclusion, the overall response rate obtained with DBDT was greater than that obtained with DTIC alone; however, this combination increases toxicity with limited impact on overall survival.

Modelling of hexadecane degradation in continuous-flow cultures.

Microorganisms of Wadden Sea sediments are able to degrade hydrocarbons in suspensions. (Berthe-Corti, L., Bruns, A., Hulsch, R., 1997. J. Microb. Methods 29, 129-137) have observed in continuous culture experiments that the growth rate of microorganisms increases roughly proportional to the dilution rate. The growth rate is nearly independent of the oxygen saturation down to about 0.5%. Even at very low oxygen supply, corresponding to an oxygen saturation far below 0.1%, growth takes place at a reduced rate. In this paper, a model is presented which can reproduce the results of these experiments. The model treats the following processes, selection of the active fraction of microorganisms growing on hexadecane, uptake of hexadecane and transformation into palmitate as a first metabolic step, synthesis of biomass, respiration and exudation. The processes are regulated by the substrate concentration, the internal palmitate quota, the exudates' concentration and an inhibiting factor. For the experiments under very low oxygen conditions, the observed growth with reduced O(2)-consumption and CO(2)-production is modelled by assuming an anoxic metabolic pathway.

Clinical and experimental evidence of Bcl-2 involvement in the response to photodynamic therapy.

PURPOSE: The role of apoptosis related proteins in the response of human malignancies to photodynamic therapy (PDT) is under investigation. The aim of the study was to examine the role of p53 and of bcl-2 protein expression in the response to PDT. MATERIALS AND METHODS: Paraffin-embedded material from 37 patients with early esophageal cancer treated with PDT (argon dye laser after intravenous injection of hematoporphyrine derivative) was studied immunohistochemically for p53 protein nuclear accumulation and bcl-2 cytoplasmic expression. Patients with residual disease after two rounds of PDT received definitive radiotherapy. In a subsequent in vitro study, W138 human lung fibroblasts and W138-SV-40 virus transformed were assessed for their sensitivity to PDT. The constitutive bcl-2 overexpression of the transformed cells vs. normal cells (assessed with RT-PCR) was 16-fold. RESULTS: Positive bcl-2 and p53 expression was noted in 10 out of 36 (27%) and 14 out of 36 (39%) patients, respectively. Seven out of 11 tumors (63%) with bcl-2 expression responded completely to PDT vs. 6 out of 26 (23%) of cases with no bcl-2 expression (p = 0.02). No association of p53, T-stage and of histology grade with response to PDT or PDT/RT was noted. The sensitivity to PDT of transformed human fibroblasts compared to normal ones was 4 times more at a fluence of 4.3 J/cm2 (4% vs. 1% cell kill) as well as at a fluence of 5.4 J/cm2 (8% vs. 2% cell kill). CONCLUSION: Bcl-2 protein expression is associated with favorable response to PDT and can be used as a predictor of cancer response to PDT. This finding can be explained by experimental studies showing that PDT induces selective degradation of the bcl-2 protein, leading to apoptosis by decreasing the bcl-2/bax ratio. Studies on PDT combination with agents targeting bcl-2 (i.e. taxanes) are on going to eventually assess a super-additive effect.

Hypoxia inducible factor (HIF-1a and HIF-2a) expression in early esophageal cancer and response to photodynamic therapy and radiotherapy.

Hypoxia inducible factor 1a and 2a (HIF-1a and HIF-2a) are key proteins regulating cellular response to hypoxia. Because the efficacy of photodynamic therapy (PDT) is dependent on the presence of oxygen, the assessment of HIF-1a and HIF-2a expression may be of value in predicting clinical response to PDT. Using recently produced MoAbs, we examined the expression of HIF1a and HIF2a in a series of 37 early-stage esophageal cancers treated with PDT and with additional radiotherapy in case of incomplete response after PDT. Strong expression of the HIF1a and of HIF2a proteins in all optical fields examined was noted in 51% and in 13% of cases, respectively. High expression was associated with a low complete response (CR) rate and with the absence of bcl-2 protein expression. On the contrary, bcl-2 expression was associated with a high CR rate. Combined analysis of HIF1a and bcl-2 protein expression revealed that of 16 cases with high HIF1a expression and the absence of bcl-2 reactivity, only 1 (7%) responded completely to PDT (P = 0.007). Bivariate analysis showed that HIF1a expression was independently related to response to PDT (P = 0.04; t ratio = 2.8), whereas bcl-2 approached significance (P = 0.07; t-ratio = 1.8). The final response to radiotherapy was high (70%) and independent of the HIF and bcl-2 status, which may be a result of reoxygenation after cellular depletion mediated by PDT. The present study suggests that assessment of HIF and of bcl-2 expression are important predictors of in vivo sensitivity to PDT. Modulation of PDT response with bioreductive drugs and/or drugs targeting bcl-2 (i.e., taxanes) may prove of significant therapeutic importance in a subgroup of patients with high HIF expression.

Composition and Activity of Marine Alkane-Degrading Bacterial Communities in the Transition from Suboxic to Anoxic Conditions.

The impact of the oxygen supply rate (OSR) on the metabolic activity and on the composition of hexadecane-degrading bacterial communities in a quasi-anoxic milieu (nominal DOT = 0%) was studied in continuous cultures containing intertidal sediment. The dilution rate was kept constant at 0.035 h-1. The OSR was stepwise reduced from 3.5 mmol O2 L-1 h-1 to 0.06 mmol O2 L-1 h-1. Activity was determined by analyzing the respiration quotient (RQ) and the rates of hexadecane degradation (QHex), of hexadecane mineralization, and of protein production (PPR). The community composition and size were investigated by fluorescence in situ hybridization (FISH), by dilution plating (colony forming units or CFU), and by most probable number (MPN). The culture showed an aerobic hexadecane metabolism down to an OSR of 0.35 mmol O2 L-1 h-1. Below this OSR, anaerobic metabolism was initiated. The relationship among the RQ, PPR, QHex, and the OSR can be approximated by hyperbola (Michaelis-Menten kinetics). We suggest that the metabolic adaptation of the culture to low OSRs is due to regulation of protein expression and enzyme activity. Reducing the OSR resulted in minor but significant changes in the concentration of different physiological and phylogenetic groups. This means that, in addition to protein expression and activity regulation, the adaptation of the population to low OSRs is due to changes in the community composition.

Muricauda ruestringensis gen. nov., sp. nov., a facultatively anaerobic, appendaged bacterium from German North Sea intertidal sediment.

A gram-negative, facultatively anaerobic bacterium with appendages was isolated from continuous cultures with a seawater-sediment suspension containing hexadecane as the sole carbon source. Although this organism was isolated from a hexadecane-degrading bacterial community, it was not able to degrade hexadecane. However, this bacterium was able to use different sugars and amino acids for growth, indicating that it probably profits from the lysis or from products like surfactants of other cells in the community. 16S rDNA analysis demonstrated that the isolated strain is phylogenetically related to the family Flavobacteriaceae of the phylum 'Cytophaga-Flavobacterium-Bacteroides'. Evidence based on phenotypic characteristics and 16S rDNA analysis supports the conclusion that this bacterium is distinct from its nearest relative, Zobellia uliginosa (90.72% similarity in 16S rRNA gene sequence), and from the other genera of the Flavobacteriaceae. It is therefore proposed that the isolated marine bacterium represents a novel taxon, designated Muricauda ruestringensis gen. nov., sp. nov. The type strain is strain B1T (= DSM 13258T = LMG 19739T).