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PubMed2003

[Can alcoholic withdrawal delirium be prevented?].

In alcohol-dependent in-patients, an adequate drug prophylaxis should be made in order to lower the degree of a developing alcohol withdrawal syndrome (AWS) or to prevent a life-threatening delirium tremens. Pre-condition of successful therapy is a precise diagnosis. In patients, the beginning of whose abstinence is known, carefully-targeted pharmacological interventions can prevent severe imbalances of neurotransmitters. Typical time courses of destabilisation of neural balances should be considered. Since there is no single drug which is able to influence various transmitter systems, normally the use of drug combinations is necessary. In ENT-patients, traumatologic patients and patients from the department of maxillo-facial surgery, screening methods based on a simply-structured questionnaire relating to information from the patient and his surroundings and selected laboratory parameters should be used. High-risk patients who could get an AWS or delirium tremens should be treated prophylactically during their oral premedication period. Important drugs for successful prophylaxis of an AWS are benzodiazepines, clonidin, magnesium and vitamin B 1. A close-meshed control of the glucose metabolism, electrolyte and acid-base balance should be performed. Neuroleptica can be used if there is any indication for their adjuvant use. In severe cases that require deep sedation or hypnosis, propofol or gamma-hydroxy-butyric acid should be used. Perioperative infusion of alcohol as a prophylactic agent against delirium tremens is regarded as an obsolete therapeutic measure for ethical reasons and because equally good or better results can be achieved by carefully-targeted drug therapy. Due to its easy use, however, the application of alcohol has not yet completely disappeared from the therapeutic spectrum.

Alcohol Withdrawal Delirium↗

PubMed2004

Imaging viable brain tissue with CT scan during acute stroke.

Viability of the cerebral parenchyma is dependent on cerebral blood flow (CBF). The assessment of cerebral perfusion in patients with acute stroke, in a clinically relevant time frame, could be of utmost importance for patient selection before thrombolytic therapy. In individual patients, quantitative mapping of CBF to indicate the severity and potential reversibility of neuronal damage can be used to predict which brain tissue will be salvaged with reperfusion or die without it (penumbra), as well as which brain tissue is already infarcted. Recent investigations of perfusion CT have shown major advances in the assessment of acute stroke patients. Perfusion CT offers a number of practical advantages over other cerebral perfusion imaging methods as it can be performed immediately after unenhanced CT, and used, in general, to exclude cerebral haemorrhage. It is fast (typical procedure time <5 min) and does not require specialized computer hardware. The accuracy of cerebral perfusion maps has been demonstrated for normal and decreased CBF value by comparison with xenon CT used as a gold standard. Perfusion CT infarct and penumbra maps provide a potential recuperation ratio (PRR) (or Lausanne Stroke Index), defined as PRR = penumbra/ (penumbra + infarct). This index is correlated with the improvement of the National Institutes of Health Stroke Scale (NIHSS) in case of arterial recanalization. Also, the size of the ischaemic area (infarct + penumbra) is correlated with the NIHSS score on hospital admission. Further studies may demonstrate the use of perfusion CT for the assessment of penumbra dynamics in function-specific brain areas. Perfusion CT is now ready to be used in clinical trials as a decision-making tool to tailor more precisely the thrombolytic therapy to the individual patient.

Brain↗

PubMed1996

[Prerequisites for effective therapy of chronic recurrent vaginal candidiasis].

67 women with chronic recurrent or persistent vaginal candidosis between 5-79 years of age were seen in our outdoor department. In 34 cases, yeasts could be isolated in a vaginal swab taken at the first consultation. On average the patients reported 5 episodes per year during the last years. Typical symptoms consisted of pruritus vulvae, local inflammation and a curdy vaginal discharge. Nearly all of the women had received local or systemic antimycotic treatment for several times. In 53% (18 patients), C. albicans had been isolated, in 29% (10 patients) C. glabrata and in 9% (3 patients) C. krusei. While candidosis due to C. albicans and C. krusei was frequently associated with distressing complaints, infections with C. glabrata caused only very few symptoms. Independent of the species, severe and persistent infections were characterized by long term persisting specific IgM-antibody-titers and remarkable lack of IgG-antibodies. The laboratory parameters of WBC, CRP and immunelectrophoresis were normal. The minimum inhibitory concentrations (MIC) of 60 Candida strains against fluconacole were determined by microdilution assay. The MIC for C. albicans (n = 35) were between 0.78 and 3.125 micrograms/ml, for C. glabrata (n = 20) between 8 and 32 micrograms/ml and for C. krusei (n = 5) between 25 and 128 micrograms/ml. In 7 cases, local antimycotic treatment was sufficient. Correlating to the sensitivity, 18 women were treated with 100-800 mg fluconacole/d for 10-20 days. In 13 of them, clearance of symptoms and yeasts was achieved. The treatment of fluconacole-resistant strains with itraconazole (100-200 ml/d for 10-20 days) together with local application of nystatin (2 x 1 Mio. IE for 10 days) was without any effect. Three women with C. albicans, C. glabrata and C. krusei infection received a candidin-vaccination (0.005 BE/ml-500 BE/ml). In all of these cases, production of IgM-antibodies was induced. However, the clinical symptoms could not be influenced. Only in two cases it was not possible to reach a clearance of symptoms and yeasts. The results show the benefit of a precise differentiation before therapy. Serologic controls of antibody titers seem to be useful tools to control the efficacy of treatment.

Adolescent↗

PubMed2001

Post-induction residual leukemia in childhood acute lymphoblastic leukemia quantified by PCR correlates with in vitro prednisolone resistance.

Most prognostic factors in childhood acute lymphoblastic leukemia (ALL) are informative for groups of patients, whereas new approaches are needed to predict the efficacy of chemotherapy for the individual patient. The residual leukemia following 4 weeks of induction therapy with prednisolone, vincristine, doxorubicin and i.t. methotrexate and the in vitro resistance to prednisolone, vincristine, and doxorubicin were measured in 30 boys and 12 girls with B (n = 34) or T lineage (n = 8) ALL. The residual leukemia was quantified after 2 (MRD-D15, n = 29) and 4 weeks (MRD-PI, n = 42) of induction therapy with a precise and reproducible clone-specific PCR technique. The median MRD-D15 and MRD-PI were 0.50% (75% range 0.0088.1%) and 0.014% (75% range 0.001-2.0%), respectively, and these levels correlated significantly (n = 29, rs = 0.75, P < 0.001). Both the MRD-D15 and the MRD-PI were related to the age of the patient (MRD-D15: rs= 0.48, P= 0.009; MRD-PI: rs = 0.45, P = 0.003). Patients with T lineage ALL had higher MRD-PI than those with B lineage ALL (median MRD-PI: 0.5% vs 0.01%, P = 0.05). The median LC50 (concentration lethal to 50% of cells) for prednisolone was 2.3 microg/ml (75% range 0.05-668). Both MRD-D15 and MRD-PI correlated significantly with the in vitro resistance to prednisolone (MRD-D15: rs = 0.41, P = 0.03; MRD-PI: rs = 0.39, P = 0.01); but not to in vitro vincristine or doxorubicin resistance. The correlations between MRD and in vitro prednisolone resistance were even more pronounced when B cell precursor and T cell leukemia were analyzed separately (B cell precursor ALL: MRD-PI vs prednisolone LC50: n = 33, rs = 0.47, P = 0.006; T cell ALL: MRD-PI vs prednisolone resistance: n = 8, rs = 0.84, P = 0.009). After a median follow-up of 5.0 years (75% range 3.2-6.9) eight patients have relapsed. All of the 21 patients with a MRD-PI < or =0.5% and a prednisolone LC50 < or =10 microg/ml have remained in remission whereas the 7 year event-free survival for the remaining 20 patients was 0.45 +/- 0.16 (P= 0.002) Prospective studies in childhood ALL are needed to clarify whether combined monitoring of in vitro drug resistance and residual leukemia early during chemotherapy could offer new ways to classify patients and stratify the intensity of therapy.

Adolescent↗

PubMed2001

[Histopathological prognostic factors in primary surgically treated cervix carcinoma].

OBJECTIVE: Standardised morphologic evaluation of radical hysterectomy specimens in primary surgically treated cervical cancer improves the selection of cases for adjuvant therapy and the precision for prognosis and may be helpful in quality control of oncologic surgery. MATERIAL AND METHODS: Following standardised macroscopic evaluation [29] the original histologic slides of all surgically treated patients with cervical cancer were searched for tumor type, histologically proven pelvic lymph node metastases (PLM), lympho-vascular space involvement (LVSI), tumor differentiation (grading), peritumoral inflammatory response, pattern of cervical wall involvement and relative depth of invasion. The results were compared with follow up. RESULTS: The frequency of patients up to 35th year of age was 28.8% and increased between 1979 and 1993 of about 10% (p > 0.05). Younger women represented more pT1 b1-tumors (55.6% vs. 47%), but without statistic significance. Contrary to advanced tumor stage and the presence of PLM, adenocarcinomatous histology (5.1% of all cases) was not associated with poor prognosis. Patients with pT1b-tumors of more than 4 cm largest extension (pT1 b2) showed a twice-fold frequency of PLM and pelvic recurrences. Five-year survival rate (5-Y-SR) decreased (82.7% vs. 64.9%) and more patients died of cancer (p = 0.005, each). Diffuse infiltration pattern was accompanied with higher rate of tumor recurrency and a shortening of 5-Y-SR compared with pushing borders at the front of infiltration, 38% versus 13.7% and 45.4% versus 75.2%, respectively. Similar was seen in poorly differentiated tumors (G3), compared with well differentiated (G1) carcinomas (recurrency: 15.1% vs. 27.5%, 5-Y-SR 75.7% vs. 59.3%; p < 0.05). Cases with the presence of LVSI, absence of peritumoral inflammatory response and deep cervical infiltration (> 66%) were accompanied with poor prognostic outcome. CONCLUSIONS: In patients with primary surgically treated cervical cancer prognostic risk evaluation can be made by standardised histopathologic handling of hysterectomy specimens. Cases with early cervical cancer and high tumor load (pT1 b2), advanced staged disease (pT2 b), histologically proven PLM, LVSI, poor tumor differentiation (G3), absence of peritumoral inflammatory response and deep cervical wall infiltration are associated with poor prognostic outcome. Patients with these morphologic patterns, which can be established by clinical examination and diagnostic biopsy, represent the clientel for adjuvant or neoadjuvant therapy.

Adenocarcinoma↗

PubMed2006

Severe eczematous skin reaction after high-dose intravenous immunoglobulin infusion: report of 4 cases and review of the literature.

BACKGROUND: High-dose intravenous immunoglobulins (IVIGs) are increasingly used to treat inflammatory and/or autoimmune disorders. In dermatology, they provide therapeutic benefit in Kawasaki disease and certain cases of dermatomyositis. While most adverse effects following IVIG treatment are not severe, occasionally more severe adverse effects occur, including anaphylactic reactions and acute, usually transient, renal failure. OBSERVATIONS: We report 4 cases of a characteristic severe extensive eczematous reaction that occurred approximately 10 days after IVIG infusion for polyradiculoneuritis. In all cases, onset was characterized by dyshidrotic lesions on the palms, rapidly followed by pruriginous maculopapular lesions involving the whole body. All patients were treated with topical and/or systemic steroids, and complete resolution of skin lesions was observed within 1 month. To date, 33 cases of cutaneous rash following IVIG infusion have been reported in the literature, mostly in neurology journals, and the features are identical to those reported herein. CONCLUSIONS: Severe eczematous skin reaction with a characteristic initial localization to the palms and/or soles that then extends to the rest of the body is a rare but characteristic adverse effect of high-dose IVIG therapy. Although the precise mechanism of this cutaneous eruption remains to be elucidated, its occurrence within days of IVIG infusion, its characteristic distribution at onset, and its clinical course should be recognized by dermatologists.

Biopsy↗

PubMed1977

Computerized cranial tomography. Effect on diagnostic and therapeutic plans.

The effect of computerized cranial tomography (CCT) on physicians' diagnostic and therapeutic plans in 194 patients scanned consecutively during a 17-day period at the Massachusetts General Hospital was studied. Use of CCT substantially decreased the perceived need for other neurodiagnostic tests in this patient population. There was a reduction of a least 41% in radionuclide scans, 52% angiograms, and 73% in pneumoencephalograms compared to the needs projected had CCT not been available. Therapy was altered after 37 scans in 36 patients (19% of those examined): new treatment was begun after 15 scans, previously planned therapy became more precise after 9 scans, treatment was found to be unnecessary after 7 scans, and treatment was abandoned as worthless after 6 scans.

Brain Neoplasms↗

PubMed1990

ACE inhibitors in renovascular hypertension.

ACE inhibition has provided many insights into the etiology and treatment of renovascular hypertension. Not only have studies using these agents profoundly expanded our understanding of the mechanisms governing preservation of renal perfusion pressures and function beyond arterial lesions, they have provided tools for more precise diagnosis and therapy in clinical practice. ACE inhibitors must be considered the agents of choice for the treatment of renovascular hypertension and provide an effective and safe medical alternative for many patients developing atherosclerotic renovascular lesions with an otherwise unacceptable risk for revascularization procedures. With the advent of widespread clinical use of these agents, however, come many new questions regarding the long-term fate of the kidney beyond vascular lesions and the need for preservation of renal function.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

[Prognosis of malignant melanoma following dissection regional lymph node metastases].

BACKGROUND: Malignant melanomas usually metastasize in the regional lymph nodes. This generally leads to a worsening of prognosis. Survival probability after extirpation of the tumorous regions is conditioned by various factors. Until now, the basis for differentiated therapy has been the precise understanding of the TNM classification. Clinical parameters are also relevant to therapy and of decisive importance to the further course of disease. QUESTION: Which clinical parameters are important to the prognosis of patients with regional melanoma and lymph node disease? PATIENTS AND METHODS: This study is a retrospective analysis of patients at the Clinic and Polyclinic of General Surgery of the University Hospital in Münster,Germany, together with a review of the literature. Included were 137 patients who received curative resection of lymph node metastases from malignant melanomas between 1974 and 1996. From the literature, 6,694 cases were found which allowed the establishment of 13 different prognosis parameters following lymph node metastasis resection These parameters were compared with our own results concerning established, relevant parameters. RESULTS: The cumulative 5-year survival rate for patients studied was 50.7%. The 5-year survival rates relating to characteristics varied between 12.9% and 80.0%. Of the 13 variables from the literature relevant to prognosis that were included in this analysis, four were found to be significant: Breslow penetration depth, standardized age and age at primary tumor diagnosis, recurrence, and location of the primary tumor. Considering these significant characteristics, one can arrive at a detailed prognostic classification of patient and history. This is indispensable for correctly tailoring therapy to disease stage.

Adult↗

PubMed2004

[OCT in macular holes].

The traditional Gass classification of macular holes can now be supplemented by additional and more detailed morphologic information obtained with optical coherence tomography (OCT). The perifoveal vitreous detachment and subsequent anterior foveal traction is considered to be the primary pathomechanism of macular hole formation. In cases of persistent traction on the fovea it may lead to foveal dehiscence. A possible explanation for intraretinal cyst formation may be secondary vitreous body fluid accumulation within the retina. A classification of macular holes based on additional information from OCT images is possible. Thus, OCT is a valuable tool for differential diagnosis of a pseudo macular hole versus macular hole, precise stage classification, therapy decision making process, outcome control after macular surgery, and prognosis prediction.

Diagnosis, Differential↗

PubMed2005

System integration and DICOM image creation for PET-MR fusion.

This article demonstrates a gateway system for converting image fusion results to digital imaging and communication in medicine (DICOM) objects. For the purpose of standardization and integration, we have followed the guidelines of the Integrated Healthcare Enterprise technical framework and developed a DICOM gateway. The gateway system combines data from hospital information system, image fusion results, and the information generated itself to constitute new DICOM objects. All the mandatory tags defined in standard DICOM object were generated in the gateway system. The gateway system will generate two series of SOP instances of each PET-MR fusion result; SOP (Service Object Pair) one for the reconstructed magnetic resonance (MR) images and the other for position emission tomography (PET) images. The size, resolution, spatial coordinates, and number of frames are the same in both series of SOP instances. Every new generated MR image exactly fits with one of the reconstructed PET images. Those DICOM images are stored to the picture archiving and communication system (PACS) server by means of standard DICOM protocols. When those images are retrieved and viewed by standard DICOM viewing systems, both images can be viewed at the same anatomy location. This system is useful for precise diagnosis and therapy.

Computer Communication Networks↗

PubMed2002

Radiofrequency bladder neck suspension for the treatment of genuine stress urinary incontinence.

Radiofrequency energy has been used for numerous medical applications including orthopedic, oncologic, and ophthalmologic indications. Characteristics of this energy source also allow it to be used for precisely controlled thermal therapy directed at soft tissues so as to induce such changes as collagen deposition and tissue shrinkage. These soft tissue effects have recently been used for the treatment of genuine stress urinary incontinence in women. As experience with this modality has matured, improved and less invasive methods of energy application have been developed. Large-scale clinical trials using this energy modality via laparoscopic and transvaginal approaches have either recently been completed or are near completion. A completely noninvasive approach is presently undergoing early clinical trials. The efficacy and safety profiles of this therapy support radiofrequency treatment of the endopelvic fascia as an option for the management of stress urinary incontinence in women.

Catheter Ablation↗

PubMed1985

Astemizole and other H1-antihistaminic drug treatment of asthma.

The disparity between the activation of mast cells in the airways of patients with allergic asthma and the lack of efficacy of H1-antihistamines in asthma therapy has been difficult to reconcile. Histamine causes bronchoconstriction when inhaled by subjects with asthma and is released in detectable amounts into the circulation after bronchial provocation with an antigen. However, it is only weakly antagonized at bronchial H1-receptors by conventional antihistamines such as chlorpheniramine and clemastine, achieving dose ratios of 2 to 4 at maximally tolerated doses. Astemizole and terfenadine are two new H1-histamine antagonists with greatly increased potency and no sedative and anticholinergic side effects. Astemizole has a delayed onset of maximal activity but induces prolonged H1-blockade that extends 15 to 30 days after the end of treatment, whereas terfenadine has a rapid onset of action with a much shorter duration of effect. With therapeutic doses (10 mg/day), astemizole is at least four times more potent in antagonizing histamine-induced bronchoconstriction than the previously available H1-antihistamines and also effectively antagonizes antigen-induced bronchoconstriction in asthma. Astemizole has been shown to be highly effective in the symptomatic treatment of seasonal allergic rhinoconjunctivitis, with the exception of nasal obstruction. With continued treatment, astemizole also offers useful protection from the symptoms of seasonal asthma. Thus the role of histamine in the pathogenesis of asthma should be reappraised. Potent H1-histamine antagonists such as astemizole and terfenadine may offer some benefit in asthma therapy, but the precise clinical indications for their use will require critical evaluation.

Astemizole↗

PubMed1992

Use of computerized hot wire block cutter in radiation therapy.

The ability to define the target volume more accurately and to deliver the radiation therapy with better precision in modern radiation oncology has resulted in radiation treatments with tighter margins in order to spare additional normal tissues. This type of treatment requires that the radiation shielding blocks be produced with high accuracy. The computer-driven block cutter has the advantage of being able to accept block contours designed from digital simulation and portal images as well as beam's-eye-view patterns produced during treatment planning. A computerized hot wire block cutter installed in our department has shown the capability to produce accurate blocks and has reduced the number of blocks requiring modifications by about one-third. The use of templates plotted on the transparencies facilitates the accurate mounting of the blocks has resulted in further reduction of the number of block modifications.

Humans↗

PubMed2006

X-ray volume imaging in image-guided radiotherapy.

Treatment simulation has significantly improved the accuracy and precision of radiation therapy delivery. A new generation of therapy systems promises to take the simulation and imaging process to a new level of accuracy; however, this will require changes in the workflow process. We describe the first generation of these devices, review the various imaging options and how they might be used in the clinic to improve treatment outcomes, and suggest several workflow approaches. Workflows discussed include on-line interventional, off-line adaptive, and off-line predictive approaches, with both geometric and dosimetric considerations. These changes will place new knowledge requirements on the medical dosimetrist and will necessitate involvement in the development of new departmental processes.

Computer Simulation↗

PubMed1999

Mesalamine blocks tumor necrosis factor growth inhibition and nuclear factor kappaB activation in mouse colonocytes.

BACKGROUND & AIMS: Derivatives of 5-aminosalicylic acid (mesalamine) represent a mainstay in inflammatory bowel disease therapy, yet the precise mechanism of their therapeutic action is unknown. Because tumor necrosis factor (TNF)-alpha is important in the pathogenesis of inflammatory bowel disease, we investigated the effect of mesalamine on TNF-alpha-regulated signal transduction and proliferation in intestinal epithelial cells. METHODS: Young adult mouse colon cells were studied with TNF-alpha, epidermal growth factor, or ceramide in the presence or absence of mesalamine. Proliferation was studied by hemocytometry. Mitogen-activated protein (MAP) kinase activation and IkappaBalpha expression were determined by Western blot analysis. Nuclear transcription factor kappaB (NF-kappaB) nuclear translocation was determined by confocal laser immunofluorescent microscopy. RESULTS: The antiproliferative effects of TNF-alpha were blocked by mesalamine. TNF-alpha and ceramide activation of MAP kinase were inhibited by mesalamine, whereas epidermal growth factor activation of MAP kinase was unaffected. TNF-alpha-stimulated NF-kappaB activation and nuclear translocation and the degradation of Ikappa-Balpha were blocked by mesalamine. CONCLUSIONS: Mesalamine inhibits TNF-alpha-mediated effects on intestinal epithelial cell proliferation and activation of MAP kinase and NF-kappaB. Therefore, it may function as a therapeutic agent based on its ability to disrupt critical signal transduction events in the intestinal cell necessary for perpetuation of the chronic inflammatory state.

Animals↗

PubMed1981

Preleukemia in children.

Six children who developed acute myelomonocytic leukemia presented with a preleukemic syndrome. The incidence of preleukemic presentation of AMML was 17% of children with acute nonlymphocytic leukemia, or 2.9% of all children with acute leukemia at this institution, incidences similar to those in adults. During the preleukemic phase, which lasted from three to 35 months, all children had anemia, all had infectious complications, and three of six had hemorrhagic tendencies. Three received steroids before the diagnosis of AMML, and all had some objective response. Two patients died before receiving therapy for AMML. Four children who received AMML therapy with combinations including cytosine arabinoside and an anthracycline achieved complete remission. Ultimately, all patients died. Clues to diagnosis of preleukemia include unexplained cytopenias, either absolute or functional, peripheral blasts, progressive megaloblastosis with an elevated B12 value, dyserythropoiesis, abnormalities of nuclear segmentation, nonrandom chromosomal alterations, and reduced marrow colony to cluster ratio in vitro. Until there is a highly effective therapy for ANLL, precisely when to treat the child with preleukemia remains uncertain. However, treatment should be started before infectious complications or hemorrhagic tendencies become life-threatening.

Adolescent↗

PubMed2002

Recent developments in inflammatory bowel disease.

The evolving medical armamentarium holds promise for more precise and effective therapies for IBD. The experience with anti-TNF therapy, particularly infliximab, illustrates the potential efficacy of therapies targeted at specific mediators or pathways involved in the pathogenesis. Advances in molecular technology have enabled the development of novel and potentially effective targeted therapies. Equally important is the increasing scientific understanding of the pathogenesis of IBD, which will likely improve the ability to stratify disease and to select therapies based on genotypic, immunologic, and phenotypic profiles in the future.

Adjuvants, Immunologic↗