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Biomedical subjects

J Lorenz

Publications and source records attributed to J Lorenz.

At least 19 recordsLinked to original sources
PubMed2006

Legionella pneumophila-induced NF-kappaB- and MAPK-dependent cytokine release by lung epithelial cells.

Legionella pneumophila causes community-acquired pneumonia with high mortality, but little is known about its interaction with the alveolar epithelium. The aim of this study was to investigate whether L. pneumophila infection of lung epithelial cells (A549) resulted in pro-inflammatory activation. L. pneumophila infection induced liberation of interleukin (IL)-2, -4, -6, -8 and -17, monocyte chemoattractant protein-1, tumour necrosis factor-alpha, IL-1beta, interferon-gamma and granulocyte colony-stimulating factor, but not of IL-5, -7, -10, -12 (p70) or -13 or granulocyte-macrophage colony-stimulating factor. The present study focused on IL-8 and found induction by L. pneumophila strains 130b, Philadelphia 1, Corby and, to a lesser extent, JR32. Knockout of dotA, a central gene involved in type IVB secretion, did not alter IL-8 induction, whereas lack of flagellin significantly reduced IL-8 release by Legionella. Moreover, p38 mitogen-activated protein kinase (MAPK) was activated and kinase inhibition reduced secretion of induced cytokines, with the exception of IL-2 and granulocyte colony-stimulating factor. In contrast, inhibition of the MAPK kinase 1/extracellular signal-regulated kinase pathway only reduced the expression of a few cytokines. L. pneumophila also induced binding of nuclear factor-kappaB subunit RelA/p65 and RNA polymerase II to the il8 promoter, and a specific inhibitor of the inhibitor of nuclear factor-kappaB complex dose-dependently lowered IL-8 expression. Taken together, Legionella pneumophila activated p38 mitogen-activated protein kinase- and nuclear factor-kappaB/RelA pathway-dependent expression of a complex pattern of cytokines by human alveolar epithelial cells, presumably contributing to the immune response in legionellosis.

Cell Culture Techniques↗
PubMed2006

A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen.

A multicentre phase II trial to determine the efficacy of vinflunine as second-line therapy in patients with advanced transitional cell carcinoma (TCC) of the bladder; secondary objectives were to assess duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients had tumours that failed or progressed after first-line platinum-containing regimens for advanced or metastatic disease, or had progressive disease after platinum-containing chemotherapy given with adjuvant or neoadjuvant intent. Response and adverse events were assessed according to WHO criteria and NCI-CTC (version 2), respectively. Out of 51 patients treated with 320 mg m(-2) of vinflunine, nine patients responded to the therapy yielding an overall response rate of 18% (95% CI: 8.4-30.9%), and 67% (95%CI: 52.1-79.3%) achieved disease control (PR+SD). Of note, responses were seen in patients with relatively poor prognostic factors such as a short (<12 months) interval from prior platinum therapy (19%, including an 11% response rate in those progressing <3 months after platinum treatment), prior treatment for metastatic disease (24%), prior treatment with vinca alkaloids (14%) and visceral involvement (20%). The median duration of response was 9.1 months (95% CI: 4.2-15.0) and the median PFS was 3.0 months (95% CI: 2.4-3.8). The median OS was 6.6 months (95% CI: 4.8-7.6). The main haematological toxicity was grade 3-4 neutropenia, observed in 67% of patients (42% of cycles). Febrile neutropenia was observed in five patients (10%) and among them two were fatal. Constipation was frequently observed (but was manageable and noncumulative) and was grade 3-4 in only 8% of patients. The incidence of grade 3 nausea and vomiting was very low (4 and 6% of patients, respectively). Neither grade 3-4 sensory neuropathy nor severe venous irritation was observed. Moreover, and of importance in this particular study population, no grade 3-4 renal function impairment was observed. Vinflunine is an active agent for the treatment of platinum-pretreated bladder cancer, and these results warrant further investigation in phase III trials, either as monotherapy or in combination with other agents as treatment of advanced/metastatic TCC of the bladder.

Adult↗
PubMed2006

[Principles and function of mechanical ventilation: classification and modes of ventilators].

A spectrum of diseases is associated with the necessity for partial or total support of pulmonary ventilation. The insight into the function of ventilators and their modes reduces the spectrum of ventilatory support to a few basic principles. The knowledge enables the pulmonary intensivist to adapt mechanical ventilation to the individual patient's needs. This overview describes the technical aspects of mechanical ventilation and summarizes the variety of specific modes implied.

Humans↗
PubMed2005

Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network.

Placebo analgesia is one of the most striking examples of the cognitive modulation of pain perception and the underlying mechanisms are finally beginning to be understood. According to pharmacological studies, the endogenous opioid system is essential for placebo analgesia. Recent functional imaging data provides evidence that the rostral anterior cingulate cortex (rACC) represents a crucial cortical area for this type of endogenous pain control. We therefore hypothesized that placebo analgesia recruits other brain areas outside the rACC and that interactions of the rACC with these brain areas mediate opioid-dependent endogenous antinociception as part of a top-down mechanism. Nineteen healthy subjects received and rated painful laser stimuli to the dorsum of both hands, one of them treated with a fake analgesic cream (placebo). Painful stimulation was preceded by an auditory cue, indicating the side of the next laser stimulation. BOLD-responses to the painful laser-stimulation during the placebo and no-placebo condition were assessed using event-related fMRI. After having confirmed placebo related activity in the rACC, a connectivity analysis identified placebo dependent contributions of rACC activity with bilateral amygdalae and the periaqueductal gray (PAG). This finding supports the view that placebo analgesia depends on the enhanced functional connectivity of the rACC with subcortical brain structures that are crucial for conditioned learning and descending inhibition of nociception.

Adolescent↗
PubMed2005

Imaging of acute versus pathological pain in humans.

Pain subserves different functions. Acute pain from the intact body alerts the victim to immediately react and withdraw from the bodily threat, ideally before an injury happens. However, during manifest injury and tissue inflammation, withdrawal and flight are no longer adaptive. Instead, sparing the affected body part to promote healing requires heightened awareness and avoidance behaviour over longer periods of time. Quality and time scales of behavioural adaptations are therefore substantially different between pain during normal compared to abnormal tissue states. Given these functional differences we postulated that the two phenomena also recruit different forebrain systems. We used positron emission tomography (PET) and subtracted scans obtained during painful heating of normal skin from scans during equally intense but normally non-painful heating of capsaicin-treated skin. This comparison reveals the specific activation of a medial thalamic pathway to limbic forebrain structures such as anterior insula, perigenual anterior cingulate, ventral striatum, and prefrontal cortex during pain originating in the chemically sensitised skin. It is possible that the unique forebrain recruitment by pain under a patho-physiological tissue status is caused by a significantly greater facilitation of the multi-synaptic projections from the spino-parabrachial tract of the superficial dorsal horn to the medial thalamus compared to deeper and direct lateral thalamic projections from the spino-thalamic tract.

Acute Disease↗
PubMed2005

[Recommendations for the treatment of respiratory complications in case of a viruspandemic].

In case of a viral pandemic without availability of effective vaccination, one can expect to be faced with additional 250 to 300 new admissions per hospital per week given the worst case scenario. Major complications are expected to occur in the respiratory system with the focus on viral pneumonia often complicated by bacterial superinfection. Frequently these patients will require artificial ventilation. The present infrastructure will not be capable of dealing sufficiently with such high numbers of casualties. These recommendations of the German Society for Pneumonology are based on the successful application of non-invasive ventilation for acute respiratory failure in recent years. It is of importance to achieve effective treatment by the use of relative simple means. The recommendation proposes to use a separate building in order to realize quarantine. In terms of diagnostic tools, a simple x-ray apparatus should be available. To monitor patients pulsoxymetry and ECG devices should be sufficient in most cases. For the treatment of acute respiratory insufficiency a sufficient number of ventilators, masks, tubing systems and filters should be kept in stock. In terms of medical treatment antibiotics to treat superinfections are of major importance. Analgesics, sedatives and intravenous fluids will also be needed. Oxygen should be available for every single patient. The recommendation gives detailed advise for the enforcement of hygiene control, diagnostic as well as therapeutic steps for in hospital treatment of high numbers of casualties of a viral pandemic.

Disease Outbreaks↗
PubMed2004

Somatotopic organization of human somatosensory cortices for pain: a single trial fMRI study.

The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. To investigate the somatotopic organization of the nociceptive system, we applied Thulium-YAG-laser evoked pain stimuli, which have no concomitant tactile component, to the dorsum of the left hand and foot in randomized order. We used single-trial functional magnetic resonance imaging (fMRI) to assess differential hemodynamic responses to hand and foot stimulation for the group and in a single subject approach. The primary somatosensory cortex (SI) shows a clear somatotopic organization ipsi- and contralaterally to painful stimulation. Furthermore, a differential representation of hand and foot stimulation appeared within the contralateral opercular--insular region of the secondary somatosensory cortex (SII). This result provides evidence that both SI and SII encode spatial information of nociceptive stimuli without additional information from the tactile system and highlights the concept of a redundant representation of basic discriminative stimulus features in human somatosensory cortices, which seems adequate in view of the evolutionary importance of pain perception.

Adult↗
PubMed2003

[Laser-evoked potentials: diagnostic approach to the dorsal root].

Functional diagnostics of the dorsal root are especially effective via nociceptive fibers on account of less intersegmental overlap compared to large-diameter fibers of the mechanoreceptive afferents. Laser-evoked potentials (LEP) are induced by short, painful heat stimuli. The aim of this work was to describe changes of the LEP in cases of dorsal root damage. The recorded LEP changes will be discussed with regard to their prognostic value as well as pathophysiologic aspects of dorsal root damage. Dorsal root function was tested in 21 patients suffering from clinically proven radiculopathy in one of the segments L4 to S1. Mechanosensibility and thermosensibility were clinically investigated. LEP were induced by slightly painful stimuli (80 on the affected and 80 on the contralateral unaffected dermatome). The LEP were evaluated by amplitude of the averaged electroencephalogram (EEG). In addition, a subjective pain rating was recorded after each stimulus. Investigation of dorsal root function by LEP in patients with radiculopathy yields two typical changes of the amplitude. On the one hand, there were significant reductions of amplitude, and on the other hand, a complete loss of LEP was found. LEP changes allow a graduation of patients who show no obvious differences in their clinical appearance. Which mechanisms are responsible as concerns deafferentiation and neuropathy of the dorsal root fibers are discussed. With regard to the LEP changes, a prognostic relevance in patients with dorsal root affections is likely. This question will be addressed in a prospective study soon.

Adult↗
PubMed2003

Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation.

Frontal lobe activity during pain is generally linked to attentional processing. We addressed the question of whether 'bottom-up' processing and 'top-down' modulation of nociceptive information dissociate anatomically within the frontal lobe by using PET scanning during painful thermal stimulation of normal and capsaicin-treated skin. We showed recently that pain following normally non-painful heat stimuli on chemically irritated skin (heat allodynia) uniquely engages extensive areas of the bilateral dorsolateral prefrontal (DLPFC), ventral/orbitofrontal (VOFC) and perigenual anterior cingulate (ACC) cortices. Here, we applied principal component analysis (PCA) and multiple regression analysis to study the covariance structure of the volumes of interest (VOI) activated specifically during heat allodynia in 14 male healthy subjects and evaluated the relationship of these VOI to ratings of pain intensity and affect. Results yielded a primary principal component (PC) that correlated positively with intensity and unpleasantness and accounted for activity in the medial thalamus, bilateral anterior insula, ventral striatum, perigenual ACC and bilateral VOFC. Activities in the right and left DLPFC loaded on separate PC and correlated negatively with perceived intensity and unpleasantness. The inter-regional correlation of midbrain and medial thalamic activity was significantly reduced during high left DLPFC activity, suggesting that its negative correlation with pain affect may result from dampening of the effective connectivity of the midbrain-medial thalamic pathway. In contrast, right DLPFC activity was associated with a weakened relationship of the anterior insula with both pain intensity and affect. We propose that the DLPFC exerts active control on pain perception by modulating corticosubcortical and corticocortical pathways.

Adult↗
PubMed2002

Evaluation of the influence of systemic neoadjuvant chemotherapy on the survival of patients treated for invasive bladder cancer.

OBJECTIVE: To assess the influence of neoadjuvant systemic chemotherapy using a modified methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) scheme in patients with invasive bladder cancer. PATIENTS AND METHODS: Two groups of patients were reviewed retrospectively; group 1 included 51 who received chemotherapy before cystectomy and group 2 included 62 who were treated only with surgery. The mean (range) duration of follow-up was 3.2 (0.25-10.25) years. The patients in group 1 were divided into two subgroups: those with tumour confined to the bladder (T1, T2 and T3a) and the remaining patients with tumour beyond the bladder (T3b, T4a,b). The chemotherapy was administered as routine MVAC, except vinblastine and methotrexate were given at 15 and 22 days during the cycle. A mean of three cycles were administered. RESULTS: The 5-year survival rate in group 1 and 2 was 66% and 58%, respectively (P > 0.3); after 8 years of follow-up the survival rates were 58% and 33%, respectively, and significantly different (P < 0.01). CONCLUSION: Systemic chemotherapy using the modified MVAC scheme in patients subsequently undergoing radical cystectomy improved the survival rate after 8 years of follow-up.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Treatment of high-risk superficial bladder cancer with maintenance bacille Calmette-Guérin therapy: preliminary results.

OBJECTIVE: To evaluate, in a prospective study, the effects and results of maintenance therapy with bacille Calmette-Guérin (BCG) in treating patients with high-risk superficial bladder cancer. PATIENTS AND METHODS: In all, 155 patients were enrolled in a randomized study of transurethral resection alone (53) or combined with intravesical BCG (102) as a treatment for superficial bladder cancer. BCG was administered for six consecutive weeks followed by three weekly instillations in months 3, 6, 12, 18, 24, 30 and 36 after resection. Recurrence, progression, prognostic factors and side-effects were assessed and analysed. RESULTS: After a median (range) follow-up of 23 (6-42) months, 83 of the 102 patients treated with BCG (81%) were disease-free, compared with 24 of the 53 treated with resection alone (45%). There was also a significant difference in tumour progression and time to progression between the trial arms. The disease progressed in eight patients (8%) treated with BCG and in 12 (23%) of those treated by resection alone. Independent risk factors for progression were DNA ploidy status and stage. Only the completion of treatment was predictive of outcome (risk of recurrence) for patients treated with BCG. CONCLUSION: Maintenance BCG therapy was better than resection alone in reducing the incidence of recurrence and progression in patients with high-risk superficial bladder cancer.

Adjuvants, Immunologic↗
PubMed2002

Quality of life in acute exacerbation of chronic bronchitis: results from a German population study.

This study reports on data from a study conducted in the Federal Republic of Germany examining the quality of life (QoL) of patients with chronic bronchitis (CB) and its acute exacerbations (AECB). Data from 320 patients were collected at AECB and subsequently during a stable phase (non-AECB) utilizing the St George's Respiratory Questionnaire (SGRQ) and the Nottingham Health Profile (NHP). As expected, the QoL of CB patients was poor, even at non-AECB, with patients reporting lower scores than patients with other chronic conditions. Patients reported significantly poorer QoL at AECB than at non-AECB. After adjusting for the severity of the underlying condition, poorer QoL at AECB was significantly and independently associated with older age, unemployment, increasing BMI, increasing number of prior AECBs, and Anthonisen AECB grade. While younger subjects reported significantly greater deterioration in QoL at AECB, the factors most consistently and independently associated with relative QoL deterioration at AECB were the number of prior AECBs and exposure to air pollution at home. In conclusion, this study highlights the detrimental effect of CB, and in particular AECB, on QoL. The association between QoL and patient reports of previous AECB number and air pollution are consistent with reports from other studies.

Acute Disease↗