Early recovery after surgery for radical cystectomy: comprehensive assessment and meta-analysis of existing protocols.

PURPOSE: Different enhanced recovery after surgery (ERAS) protocols (EP) for radical cystectomy (RC) have been published. Protocols highly differ in number of included items and specific measures. MATERIALS AND METHODS: A systematic review and meta-analysis on EPs in RC were performed using the databases MedLine, Cochrane Library, Web of science, and Google Scholar. The specific ERAS measures of the protocols were extracted, analyzed, and compared. Pooling of available outcome data was performed for length of stay, complications, readmission rate, and time to defecation. RESULTS: The search yielded a total of 860 studies of which 25 studies were included in qualitative and 22 in quantitative analysis. Oral bowel preparation (BP) was omitted in 24/25 (96%) EPs, optimized fluid management was administered in 22/25 (88%) EPs and early mobilization (postoperative day 1) in 21/25 (84%). Gum chewing (n = 12, 46%), metoclopramide (n = 11, 44%), and alvimopan (n = 6, 24%) were the most common measures to prevent postoperative ileus. Our meta-analysis revealed a significant benefit in favor of EPs for the outcome parameters length of stay [mean difference (MD) - 3.46 d, 95% confidence interval (CI) - 4.94 to - 1.98, p < 0.01], complications [Odds ratio (OR) = 0.76, 95% CI 0.61-0.94, p = 0.01] and time to defecation (MD - 1.37 d, 95% CI - 2.06 to - 0.69, p < 0.01). Readmission rate did not show a significant difference (OR = 0.73, 95% CI 0.52-1.03, p = 0.07). CONCLUSION: Current EPs focus on omitting oral BP, early mobilization, and optimized fluid management while they differ in methods preventing postoperative ileus. Our meta-analysis revealed a benefit in introducing these protocols into clinical practice.

[Rates of prostate-specific antigen testing for early detection of prostate cancer: a first comparison of German results with current international data]. / PSA-basierte Früherkennung des Prostatakarzinoms durch den Hausarzt: Erste deutsche Ergebnisse im internationalen Vergleich.

OBJECTIVE: Measurement of prostate-specific antigen (PSA) is not only used as a screening instrument by urologists, but also by general practitioners and internal specialists (GP-IS). Until now, there are neither data on the approach of German GP-IS in practicing this nor have data been classified in the context of available international literature on this topic. MATERIALS AND METHODS: Between May and December 2012, a questionnaire containing 16 items was sent to 600 GP-IS in Brandenburg and Berlin. The response rate was 65% (392/600). Six indicator questions (IQ1-6) were selected and results were set in the context of available international data. The quality of present studies was evaluated by the Harden criteria. RESULTS: Of the 392 responding physicians, 317 (81%) declared that they would use PSA testing for early detection of PCA (IQ1) and, thus, formed the study group. Of these GP-IS, 38% consider an age between 41 and 50 years as suitable for testing begin (IQ2), while 53% and 14% of the GP-IS perform early detection until the age of 80 and 90 years, respectively (IQ3). A rigid PSA cut-off of 4 ng/ml is considered to be reasonable by 47% of the involved GP-IS, whereas 16% prefer an age-adjusted PSA cut-off (IQ4). Patients with pathological PSA levels were immediately referred to a board-certified urologist by 69% of the GP-IS. On the other hand, 10% first would independently control elevated PSA levels themselves after 3-12 months (IQ5). Furthermore, 14% of the interviewed physicians consider a decrease of PCA-specific mortality by PSA screening as being proven (IQ6). Knowledge regarding PCA diagnostics is mainly based on continuous medical education for GP-IS (33%), personal contact with urologists (6%), and guideline studies (4%). While 53% indicated more than one education source, 4% did not obtain any PCA-specific training. The results provided by this questionnaire evaluating response of German GP-IS to six selected indicator questions fit well into the international context; however, further studies with sufficient methodical quality are required. CONCLUSIONS: Despite current findings and controversial recommendations of the two large PCA screening studies on this issue, German GP-IS still frequently use PCA screening by PSA measurement. Primary strategies of early detection as well as follow-up after assessment of pathologically elevated PSA levels poorly follow international recommendations. Thus, an intensification of specific education is justified.

[Preventive advice-giving: self-assessment of general practitioners in Brandenburg]. / Präventive Beratung: Selbsteinschätzungen Brandenburger Hausärzte.

INTRODUCTION: Improving individual health behaviour is a promising approach especially in cardiovascular prevention. In general practice, preventive advice-giving is hitherto put into practice insufficiently. The study explores which role general practitioners are willing and able to play in behaviour-oriented prevention. METHODS: 50% of general practitioners in Brandenburg (n=748) were randomly selected for the study. A standardised questionnaire was mailed to them in which their attitudes towards preventive advice-giving were measured using Likert scaling. Participation was anonymous. RESULTS: 37% of the physicians answered the questionnaire. Almost all of them see it as their responsibility to inform patients about possible reduction of lifestyle-dependent health risks and to motivate them accordingly. Self-assessment concerning advisory skills is predominantly positive (best for physical activity, worst for smoking cessation and sexual risk behaviour advice). Time resources for behaviour-oriented prevention are sparse. For this reason, the delegation of many advisory tasks to physician assistants is regarded positively. CONCLUSION: Most physicians see themselves as willing and able to perform behaviour-oriented prevention. Nevertheless, realising this task seems to be difficult, e. g., concerning the frame conditions of general practice. The role of general practitioners in prevention and health promotion should be defined more accurately.

Counseling overweight patients: analysis of preventive encounters in primary care.

OBJECTIVE: The increasing prevalence of obesity requires particularly primary care providers to take action. The aim of this study was to analyze general practitioners (GPs) encounters with overweight and obese patients in primary care to test the hypothesis that patients with a BMI ≥ 30 kg/m² would have longer consultations focusing on lifestyle-related issues like nutrition and physical activity than those with a BMI < 30 kg/m². DESIGN: Cross sectional comparison of audiotaped encounters of patients with a BMI ≥ 30 kg/m² and those with a BMI < 30 kg/m². SETTING: Twelve GP surgeries in Berlin, Germany. PARTICIPANTS: Fifty patients who agreed to have preventive check-up encounters audiotaped. MAIN OUTCOME MEASURES: Based on the Roter Interaction ANALYSIS: System (RIAS) we assessed duration of encounter and the prevalence of GP statements regarding cardiovascular risks, nutrition and physical activity. RESULTS: An increased BMI was found to be a predictor for the length of encounters (P = 0.01), whereas the content of talks was mainly determined by the individual of GP and sex of the GP. Statements regarding cardiovascular risks were most frequent, followed by those regarding nutrition and physical activity. In this study the assessed physiological parameters were not associated with the specific contents of preventive encounters like nutrition or physical activity (P > 0.05). CONCLUSIONS: Our results indicate that GPs rarely use the check-up program to conduct lifestyle consultations with obese patients. Barriers to lifestyle counseling and possible solutions are discussed with a view to promoting individualized and target management of overweight patients.

[Treatment of rectal carcinoma: satisfaction of general practitioners with surgical clinics]. / Operative Therapie des Rektumkarzinoms: Zufriedenheit des Hausarztes mit der chirurgischen Klinik.

AIM: The present study aimed to analyze the satisfaction of referring general practitioners with the surgical departments concerned with further treatment of patients regarding cooperation and therapeutic results. PATIENTS AND METHODS: A total of 442 general practitioners were interviewed about a total of 601 patients by a standardized questionnaire. The return rate was 63.1% and 73.4% of questionnaires could be analyzed. The study group (SG) comprised 265 patients with rectal carcinoma, who were treated by 204 general practitioners and in 17 different hospitals. The mean age at the time of surgery was 67.8 years. RESULTS: The oncological result represented the decisive the crucial criterion regarding therapeutic satisfaction of the general practitioners. Postoperative erectile function was the least satisfying parameter, although its priority was considerably more dispensable than the oncological result. Regarding cooperation with the hospital, the content of the epicrisis was the most satisfying parameter. The value of a sufficient and furthermore contemporarily forwarded epicrisis was categorized as very important. CONCLUSION: Telephone availability, waiting period until in-patient admission and content of the epicrisis were assessed positively. The main point of criticism was the timely receipt of the epicrisis. The surgical expertise regarding the treatment of rectal carcinoma was assessed as the main quality parameter of the hospital.

The pyridinylfuranopyrimidine inhibitor, PI-103, chemosensitizes glioblastoma cells for apoptosis by inhibiting DNA repair.

The failure of conventional therapies in glioblastoma (GBM) is largely due to an aberrant activity of survival cascades, such as PI3 kinase (PI3K)/Akt-mediated signaling. This study is the first to show that the class I PI3K inhibitor, PI-103, enhances chemotherapy-induced cell death of GBM cells. Concurrent treatment with PI-103 and DNA-damaging drugs, in particular doxorubicin, significantly increases apoptosis and reduces colony formation compared with chemotherapy treatment alone. The underlying molecular mechanism for this chemosensitization was shown by two independent approaches, that is, pharmacological and genetic inhibition of PI3K, DNA-PK and mTOR, to involve inhibition of DNA-PK-mediated DNA repair. Accordingly, blockage of PI3K or DNA-PK, but not of mTOR, significantly delays the resolution of doxorubicin-induced DNA damage and concomitantly increases apoptosis. Importantly, not only are several GBM cell lines chemosensitized by PI-103 but also GBM stem cells. Clinical relevance was further confirmed by the use of primary cultured GBM cells, which also exhibit increased cell death and reduced colony formation on combined treatment with PI-103 and doxorubicin. By identifying class I PI3K inhibitors as powerful agents in enhancing the lethality of DNA-damaging drugs, to which GBMs are usually considered unresponsive, our findings have important implications for the design of rational combination regimens in overcoming the frequent chemoresistance of GBM.

[The assessment of pathological PSA values by the general practitioner--observation or intervention?]. / Die Bewertung pathologischer PSA-Werte durch den Hausarzt--Beobachten oder Handeln?

AIM: The aim of the present study was to evaluate the initiated consecutive diagnostic course after measurement of an elevated PSA value by the general practitioner. PATIENTS AND METHODS: 406 patients who underwent ultrasound-guided transrectal biopsy of the prostate were assessed retrospectively. Using a standardised questionnaire, we evaluated the examination findings detected by the general practitioners responsible for the patients' medical care. RESULTS: 88 patients revealed an elevated PSA-value of > or = 4 ng / mL. 60 of these patients showed an elevated PSA already in the first measurement. 36 patients underwent repeated measurement of PSA performed by the general practitioner. In 4 of these 36 patients an elevated PSA level had al-ready been measured in a previous analysis, and, therefore, repeated measurement was performed in the follow-up. The median time interval between assessment of the pathological PSA value and prostate biopsy amounted to at least 20 weeks in the case of a pathological PSA value in the first measurement and up to a maximum of 43 weeks in the case of a further control of an already increased PSA value. Altogether 47 cases of prostate cancer were detected. In 40 of these patients with histologically proven prostate cancer, the pathological PSA value had previously been assessed by the general practitioner. CONCLUSION: In the majority of cases, an elevated PSA value resulted in a contemporary diagnostic course using transrectal biopsy of the prostate. In particular cases a further control measurement of PSA was accomplished, which resulted in an unacceptable delay regarding the histological confirmation of the diagnosis.

[The significance of rebiopsy in the diagnosis of prostate cancer]. / Stellenwert der Rebiopsie in der Diagnostik des Prostatakarzinoms.

OBJECTIVE: The objective of this study was to evaluate whether rebiopsy of the prostate leads to a significant increase in the detection rate of prostate cancer compared with performing a single biopsy. METHODS: Data from 406 patients were evaluated retrospectively. The patients had undergone ultrasound-guided transrectal biopsy of the prostate between January 2004 and August 2005. Besides demographic data, the patient information was reviewed with regard to the number of biopsy samples taken per patient, histological results, and the occurrence of complications during or after the examination. If prostate cancer was detected, data acquisition included the number of positive biopsy samples taken per examination as well as the subsequent therapy and the TNM classification of the tumor. After a follow-up time between 24 and 42 months, all patients with a histologically negative first biopsy were reevaluated regarding rebiopsy. We evaluated the follow-up time (in months) and the histological results. If prostate cancer was detected, we assessed the number of positive biopsy cores as well as the subsequent therapy and the TNM classification. RESULTS: In 37.7% of all patients (n=153), prostate cancer was detected in the first biopsy. In 56.9% of these (n=87), a high-grade carcinoma with a Gleason score >or=7 was diagnosed. In 108 patients, a second biopsy was performed. The mean time between the first biopsy and rebiopsy was 21.7 months (range 1.3-41.2 months). With the second biopsy, prostate cancer was detected in 29 cases (26.9%), of which 51.7% (n=15) showed a high-grade carcinoma. There was no significant difference between the first biopsy and the second biopsy concerning either the detection rate of carcinomas related to the total number of transrectal multibiopsies or the detection of high-grade carcinomas related to the number of detected carcinomas. Provided that values beyond the second standard deviation were excluded from analysis, prostate-specific antigen (PSA) values at the time of rebiopsy were significant elevated compared with PSA values at the time of first biopsy. More than two-thirds of all patients with a histologically positive result in the second biopsy revealed a PSA velocity >or=0.6 ng/ml/year. Furthermore, there was no significance between the number of histologically positive samples per multibiopsy when prostate cancer was diagnosed in the first biopsy compared with the number of positive samples in the second biopsy. Complications after biopsy were noted in 19 patients. In three cases, hospitalization was necessary. CONCLUSION: As a result of performing a rebiopsy, the detection rate of prostate cancer increased significantly compared with the detection rate after a single biopsy. Thus, the number of patients who could receive therapy was also increased. Due to the relatively low complication rate of prostate multibiopsy, this examination can be widely indicated. There was not a higher detection rate of high-grade prostate cancer in the second biopsy compared with performing only a single biopsy. The indication for a second biopsy as well as the determination of the time interval between the first and second biopsy should consider the current PSA value and PSA dynamics. Therapeutic consequences should also be taken into consideration. In the event of a PSA velocity >0.6 ng/ml/year, a rebiopsy should definitely be performed.

[The general practitioner's part in the initiation of diagnostic procedures in prostate cancer]. / Die Rolle des Hausarztes bei der Initiierung der Diagnostik des Prostatakarzinoms.

AIM: The aim of the study is the analysis of diagnostic procedures performed by general practitioners (GPs) leading to the detection of prostate cancer (PCA). PATIENTS AND METHODS: A retrospective evaluation was performed on all 406 patients who underwent ultrasound-supported transrectal multibiopsy of the prostate in our department between January 2004 and August 2005. The GPs were interviewed by use of standardised questionnaires concerning the indication for specific examinations, referrals to the specialist, the clinical findings and results, and the GPs own urological qualification. The rate of returned questionnaires was 72.9 % (105 of 144 GPs), therefore a study group (SG) of 295 patients (72.7 %) was formed. The mean age was 67.2 (40 - 90) years. RESULTS: In 190 patients (64.4 %) primary diagnostic measures were performed by the GP herself/himself. All the other patients had already been in urological specialist treatment (n = 43), were either referred directly to an urologist for primary diagnostics (n = 42) or were diagnosed during a hospital stay (n = 3). The reasons for the performed diagnostic measures were not to be found in 17 cases. In 50.8 % of all cases the initiation of preventive medical check-ups or determination of PSA levels was done at the patient's own request. 91 of 176 digital rectal examinations (DRE) performed by GPs showed suspect findings, leading to referral to the urologist in 62 cases. PSA levels of 105 patients measured by the GPs ranged between 0.0 and 1662 ng/mL with a mean level of 29.81 and a median of 6.20 ng/mL. In 75 cases the PSA level led to a referral to the urologist. In the case of 27 patients the referral was decided because of clinical symptoms. In 39.0 % (n = 115) of the SG a PCA was detected by biopsy. In 43.0 % (n = 64) of the patients originally examined by the GPs the suspected diagnosis of a PCA based on a pathological PSA level and/or DRE proved to be correct. The GPs stated in 35.2 % (n = 37) that they had spent a certain period of time in a urological department during their medical training. Concerning referrals and the positive predictive value of DRE, there was no statistically significant different to be found in GPs without urological training. CONCLUSION: Every fifth patient in the study group showed a histologically proven PCA that had initially been suspected by a GP based on a pathological PSA level and/or DRE. This underlines the value of preventive exams in the hands of GPs. In addition, the correct and sensible use of PSA levels controls by GPs as well as a pronounced desire for preventive medical check-ups on the patient's side was shown.

Neurosurgical management of previously coiled recurrent intracranial aneurysms.

OBJECTIVE: Endovascular treatment of cerebral aneurysms with detachable coils has proven to be a save and effective treatment. But long-term recurrence due to aneurysm regrowth or coil compaction has been reported in up to thirty percent of cases. Therefore a growing number of previously coiled aneurysms have to be retreated by coiling or, in some circumstances, by clipping. We present a consecutive series of ten patients who underwent surgical clipping for recurrent aneurysms after primary coil embolization. METHODS: During a 4-year period ten patients with intracranial aneurysms previously treated by coil embolization underwent surgery for clipping of recanalized aneurysms. All aneurysms were located in the anterior circulation (internal carotid artery [ICA], 2; middle cerebral artery [MCA], 3; anterior communicating artery [AcomA], 5). Clinical data and imaging studies of the patients were analyzed retrospectively. RESULTS: All recurrences were detected by routine control angiograms within a median period of 14 months after primary treatment. In three aneurysms treated for SAH dense arachnoid scarring around the aneurysm sac was noted. In four cases, coils were found intraoperatively to be extruding through the aneurysm sac into the subarachnoid space. Each aneurysm could be clipped without affecting the perfusion of the parent vessel. In one patient the aneurysm sac including the coil package was resected. In one patient one of the central anteromedial arteries was injured during dissection due to dense arachnoid scarring because of prior SAH. As a consequence infarction of the head of the caudate nucleus without neurological compromise was observed on follow-up CT scans. Another patient developed transient aphasia due to vasospasm in the early postoperative period with complete restitution. In the end all patients had an uneventful recovery. Removal of the coil package was not necessary in most cases. Clipping of the aneurysm neck was possible even in cases with coil dislocation into the parent vessel. CONCLUSION: Clipping of previously coiled aneurysms is a unique problem for vascular neurosurgeons. In most cases clipping is feasible. Clipping should still be considered as a definite treatment option in previously coiled recurrent aneurysms. Results in this small series were good.

Brain tumour surgery in the vicinity of short-term memory representation--results of neuronavigation using fMRI images.

OBJECTIVE: Functional information concerning the surrounding brain is mandatory for a good clinical outcome in brain tumour surgery. The value of fMRI to detect the motorcortex and Broca's area is widely accepted today. If an appropriate paradigm is used, short-term memory areas can be visualized as well. Obviously this information must be integrated into cranial neuronavigation for an appropriate intra-operative use. We report our first experiences with the direct integration of short-term memory fMRI into cranial neuronavigation. METHOD: From January 2001 to March 2002 14 patients were operated on for intracranial tumours with short-term memory fMRI imaging, using the "two-back-paradigm". Both pre- and postoperatively, the short-term memory of all patients was tested additionally by a standardized test battery including 16 different verbal and visuo-spatial items. RESULTS: In all 14 patients the general level of working memory capacity was preserved after surgery. The visuo-spatial performance was kept unchanged or deteriorated slightly, the alertness slightly worsened as well, but we found an improvement in verbal test items. CONCLUSION: The two-back paradigm is able to visualize verbal memory tasks in fMRI. For visuo-spatial items, a new paradigm has to be designed. In contrast to deep seated brain lesions, focal cortical impairments do not lead to obvious and serious memory deficits. Therefore, the aim of gross total tumour removal has to be balanced against the aim of preservation of short-term memory fields. Nevertheless, the knowledge of the localization of cortical short-term memory fields may combine both aims during navigated brain tumour surgery, thus preserving the patient with a better quality of life.

[Management of iatrogenic lesions of the spinal accessory nerve]. / Management iatrogener N.-accessorius-Läsionen.

Lesions of the spinal accessory nerve are usually iatrogenic, especially after lymph node extirpation on the neck. Between 1994 and 2003, 31 patients were operated on in the Neurosurgical Department of the University of Ulm for iatrogenic lesions of the XIth cranial nerve. Of 31 patients, 22 had undergone a previous lymph node extirpation, 2 had been injured during a selective peripheral denervation for spasmodic torticollis, and the other 7 patients by different causes. The neurosurgical intervention was performed 0-19 months after trauma (mean 7.2 months). All patients showed paresis/atrophy of the trapezius muscle, and the abduction of the shoulder was markedly reduced. Additional neck and/or shoulder pain was present in 29 of 31 cases. In seven cases, the nerve was compressed by scar tissue and subsequently treated by external neurolysis. Ten patients underwent an end-to-end anastomosis; autologous sural nerve grafting was necessary in 13 cases. After a mean follow-up of 12.6 months, 7 of 31 patients completely recovered. Of 31 patients, 19 experienced partial relief of pain and weakness. Only five patients remained unchanged. The clinical findings after autologous nerve grafting, end-to-end reconstruction, or external neurolysis did not show any significant differences. Microsurgical reconstruction of iatrogenic injury of the spinal accessory nerve is very promising if the interval between trauma and surgical revision is less than 6 months. Up to 12 months, partial recovery can be achieved. Outcome after longer delay is unsatisfactory.

Lipomas of the internal auditory canal--report of two cases and review of the literature.

OBJECTIVE: Lipomas of the internal auditory canal are extremely rare. So far, only 21 cases have been described in the literature. We present here two of our own cases and review the literature to date with special emphasis on the diagnostic and therapeutic options. METHOD: During the last seven years two lipomas of the internal auditory canal were surgically treated in our department. Despite native and gadolinium-enhanced MRI and a thin-sliced temporal bone CT scan they were misdiagnosed as intracanalicular acoustic neurinomas. RESULTS: Total tumour removal could be achieved, the facial nerve function was conserved, but both patients were rendered functionally deaf after surgery. CONCLUSION: Lipomas' radiological behaviour may mimic acoustic neurinomas; without fat-suppressed T(1)-weighted images they are often preoperatively misdiagnosed as acoustic neurinomas. Although the postoperative morbidity with respect to cochlear and facial nerve function is much higher than in small acoustic schwannomas, early surgery may be justified, because complete removal is only possible in this stage. No reliable data are available concerning the natural history of this kind of lesion.

[Costs of ambulant care for patients with inflammatory bowel disease in general practice]. / Kosten der allgemeinmedizinischen Versorgung von Patienten mit chronisch-entzündlichen Darmerkrankungen.

BACKGROUND: Outpatient care managed by general practitioners plays an important role in diagnostic and treatment of inflammatory bowel diseases (IBD). The chronic recurrent course often requires intensive and costly medical care. OBJECTIVE: To measure the costs of outpatient care for patients with IBD provided by general practitioners (GPs). MATERIAL AND METHODS: The analysis is based on an electronic data base implemented in 100 general practices in different parts of Germany. 191 patients with altogether 705 consultations over a period of one year were included in the analysis. Costs of care were measured using German fee schedules for health care delivery and market prices for drugs. RESULTS: In a 12-months-period the mean number GP-contacts was 3.6. Mean costs were 23.61 euro; per visit and annual costs were 87.15 euro; per patient. Pharmacotherapy was used by 147 patients (77%) and caused costs of 613.40 euro; per year, with 64% due to the use of salicylates. 66 patients (35%) also had diagnostic services provided from specialists, 7 patients (4%) required psychotherapeutic care. CONCLUSION: The presented study is the first to analyse in detail the costs for medical care of IBD in general practices in Germany. Results can be used in economic assessment of the disease and in cost-effectiveness-analyses of intervention strategies. They may support treatment guidelines and treatment decisions from an economic point of view.

Cranial neuronavigation with direct integration of (11)C methionine positron emission tomography (PET) data -- results of a pilot study in 32 surgical cases.

BACKGROUND: MRI detects small intracranial lesions, but has difficulties in differentiating between tumour, gliosis and edema. (11)C methionine-PET may help to overcome this problem. For its appropriate intra-operative use, it must be integrated into neuronavigation. We present the results of our pilot study with this method. METHOD: 32 patients with 34 intracranial lesions detected by MRI underwent additional (11)C methionine-PET, because the pathophysiological behaviour or the tumour delineation was unclear. All lesions were treated surgically. In 25 patients PET data could be integrated directly into cranial neuronavigation. FINDINGS: (11)C methionine uptake was observed in 27/34 lesions, 26 of them were tumours: 14 malignant and 7 benign gliomas, 3 gliomas without further histological typing, one Ewing sarcoma and one non-Hodgkin lymphoma. Only one (11)C methionine positive lesion was non-tumourous: it was staged as post-irradiation necrosis in a patient operated on for a malignant glioma. 3/7 (11)C-methionine negative lesions were classified as gliosis (n=2) and M. Whipple (n=1), but 4/7 were tumours: 2 astrocytomas WHO(degrees)II, 1 DNT and one astrocytoma WHO(degrees)III. The sensitivity of (11)C methionine-PET was 87%, the specificity 75%, the positive predictive value 96% and the negative predictive value 43%. In all tumourous cases with positive tracer uptake the borderline area of the tumour was better defined by (11)C methionine-PET than by MRI. INTERPRETATION: A positive (11)C methionine-PET is highly suspicious of a tumour, a negative one does not exclude it. (11)C methionine-PET seems to be more sensitive than MRI for differentiating between tumour and edema or gliosis. Simultaneous integration MRI and (11)C methionine-PET into cranial neuronavigation can facilitate cross total tumour removal in glioma surgery.

In vivo synthesis of the periplasmic domain of TonB inhibits transport through the FecA and FhuA iron siderophore transporters of Escherichia coli.

The siderophore transport activities of the two outer membrane proteins FhuA and FecA of Escherichia coli require the proton motive force of the cytoplasmic membrane. The energy of the proton motive force is postulated to be transduced to the transport proteins by a protein complex that consists of the TonB, ExbB, and ExbD proteins. In the present study, TonB fragments lacking the cytoplasmic membrane anchor were exported to the periplasm by fusing them to the cleavable signal sequence of FecA. Overexpressed TonB(33-239), TonB(103-239), and TonB(122-239) fragments inhibited transport of ferrichrome by FhuA and of ferric citrate by FecA, transcriptional induction of the fecABCDE transport genes by FecA, infection by phage phi80, and killing of cells by colicin M via FhuA. Transport of ferrichrome by FhuADelta5-160 was also inhibited by TonB(33-239), although FhuADelta5-160 lacks the TonB box which is involved in TonB binding. The results show that TonB fragments as small as the last 118 amino acids of the protein interfere with the function of wild-type TonB, presumably by competing for binding sites at the transporters or by forming mixed dimers with TonB that are nonfunctional. In addition, the interactions that are inhibited by the TonB fragments must include more than the TonB box, since transport through corkless FhuA was also inhibited. Since the periplasmic TonB fragments cannot assume an energized conformation, these in vivo studies also agree with previous cross-linking and in vitro results, suggesting that neither recognition nor binding to loaded siderophore receptors is the energy-requiring step in the TonB-receptor interactions.

Iron uptake mechanisms and their regulation in pathogenic bacteria.

In the human body iron is present in growth-limiting amounts for bacteria. For this reason intricate iron transport and iron regulatory systems evolved in bacteria to guarantee a sufficient iron supply. The few principal mechanisms that underly the large variety of iron supply systems will be presented, as well as cases, in which defined iron supply systems are related to virulence.

Evaluation of iatrogenic lesions in 722 surgically treated cases of peripheral nerve trauma.

OBJECT: The purpose of this study was to discover the number and types of iatrogenic nerve injuries that were surgically treated during a 9-year period at a relatively busy nerve center. The specific nerves involved, their sites of injury, and the mechanisms of injury were also documented. METHODS: The authors retrospectively evaluated the surgically treated iatrogenic lesions by reviewing case histories, operative reports, and follow-up notes in 722 cases of trauma. These cases were treated between January 1990 and December 1998 because of pain, dysesthesias, and sensory and/or motor deficits. latrogenic injury was a much larger category of trauma than predicted. One hundred twenty-six (17.4%) of the 722 surgically treated cases were iatrogenic in origin. Most of these injuries occurred during a previous operation. To a major extent, nerves of the extremities were affected, and a relatively large number of injuries occurred in the neck and groin. Incidence was highest in the spinal accessory nerve (14 cases), the common peroneal nerve (11 cases), the superficial radial nerve (10 cases), the genitofemoral nerve branches (10 cases), and the median nerve (nine cases). At least two thirds of the patients did not undergo surgery for the iatrogenic injury within an optimal time interval due to delayed referral. Follow-up data were available in 97 of the 126 patients. Surgical outcomes demonstrated improvement in 70% of patients. Operative results were especially favorable in patients suffering from iatrogenic injuries to the accessory and superficial sensory radial nerves. CONCLUSIONS: latrogenic injuries should be corrected in a timely fashion just like any other traumatic injury to nerve.

Case reports of symptomatic metastases in four patients with primary intracranial gliomas.

Four patients with primary intracranial high-grade gliomas are reported. Three of them developed spinal symptoms and signs generated by spinal metastases a few months after first diagnosis, the last patient developed an extraspinal metastasis in cervical lymph nodes. The spinal metastasis of a 30 years old patient was located intradurally at L5/S1, in the second patient at level L3, the third patient presented with multiple metastases in the cervical, thoracic and lumbar spine. Previously reported cases are reviewed, are discussed in the light of our own observations and analysed for the various therapeutic options.