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Biomedical subjects

H Hirche

Publications and source records attributed to H Hirche.

At least 55 records · Page 3Linked to original sources

High cytoplasmic Ca2+ levels reached during Ca(2+)-induced Ca2+ release in single smooth muscle cell as reported by a low affinity Ca2+ indicator Mag-Indo-1.

The low-affinity Ca2+ indicator Mag-Indo-1 was used to measure increments of ionised Ca2+ concentration in the cytoplasm of single smooth muscle cells isolated from guinea-pig urinary bladder. With 3.6 mM [Ca2+]o, depolarization steps to 0 mV were associated with a transient increase of fluorescence ratio (F410/F470) only when Ica triggered a Ca(2+)-induced Ca2+ release (CICR). [Ca2+]i transiently peaked to 3-5 microM and despite continuous Ca2+ influx the [Ca2+]i signal fell close to the baseline. Rapidly applied caffeine (10 mM) increased [Ca2+]l by 16 microM, the response was completely blocked by intracellular ryanodine (20 microM). With ryanodine intracellularly, Ica produced very small [Ca2+]i signals unless it was augmented by elevation of [Ca2+]0 to 10 mM and addition of 1 microM Bay K8644. Under these conditions, [Ca2+]l responded with a tonic elevation lasting as long as the depolarizing pulse. It is concluded that the low-affinity indicator Mag-Indo-1 reports predominantly Ca2+ release from SR in cytoplasm.

Animals↗

Effects of varying filter kernel sizes on the image quality of interstitial lung diseases.

PURPOSE: The aim of the study was to optimize the postprocessing of digital luminescence radiographs of interstitial infiltrates of the lung. MATERIAL AND METHODS: Ninety-seven patients with established diseases of the lung parenchyma were examined: 514 pathological details were investigated, using a 200-speed screen-film system and a storage phosphor plate. In digital postprocessing, the size of the filter kernel (S) varied between S 5 and S 70. Based upon 32896 individual evaluations, the image quality was evaluated in multifactorial variance analyses. RESULTS: The digital standards were significantly inferior to the tested screen-film system. The large filter kernel S 70 and the small filter kernels S 5 and S 10, as well as an algorithm for edge enhancement, showed selective advantages in the depiction of nodular or small linear structures. For micronodular and linear structures, kernel sizes of S 20 and S 40 produced equally good results (p > 0.05). CONCLUSION: Whenever optimized postprocessing is involved, storage phosphor radiography is equal to a modern screen-film system and can be substituted for the latter without any loss of image quality; this is especially valid for the imaging of interstitial infiltrates of the lung.

Female↗

ROC-analysis of detection performance by analogue and digital plain film systems in chest radiography.

PURPOSE: To compare the performances of 4 imaging systems in the diagnostic radiology of the chest: an asymmetric screen-film combination (a-SFC); a conventional screen-film combination of speed class 200 (SFC); a screen-film combination of speed class 200 with an aluminium lung filter; and digital luminescence radiographs (DLR). MATERIAL AND METHODS: Object detectability studies were carried out using an anthropomorphic chest phantom. The images were obtained under standard exposure conditions at 125 kVp. The detection performance of the various systems was evaluated by receiver operating characteristic (ROC) analysis on the basis of a total of 12,240 observations. RESULTS: In the overall evaluation the a-SFC and the SFC plus lung filter received equally high ratings of 0.878+/-0.018 and 0.860+/-0.21, respectively (p>0.05). There was no significant difference between the 200-speed SFC and the storage phosphor radiographs. In the mediastinum all the tested systems were clearly superior to the 200-speed SFC (p<0.05) while in the lung fields the 200-speed SFC received a high rating of 0.866+/-0.026. The a-SFC had slight advantages over the SFC plus lung filter and the 2 digital imaging modes (p>0.05). CONCLUSION: The a-SFC and the digital luminescence radiographs provide a significant gain in diagnostic information in the mediastinum without diminishing detail detectability in the lung fields and without additional radiation exposure.

Filtration↗

Epirubicin and ifosfamide in metastatic breast cancer.

In a randomized, phase II trial, we evaluated the effectiveness of continued chemotherapy with epirubicin/ ifosfamide versus unmaintained treatment interruption in advanced metastatic breast cancer. Three hundred fifty-seven patients were enrolled and 331 were evaluable for response. Complete response was achieved in 25 patients (8%) and partial response in 121 patients (37%). Pretreatment status correlated significantly with response (complete and partial response). While 54% of unpretreated patients responded, only 42% of the patients responded who had been pretreated with adjuvant chemotherapy and 33% who had been pretreated in the metastatic stage of disease; 69 patients (21%) had disease progression. Of 11 patients pretreated in both the adjuvant and metastatic setting, only two responded. Toxicity of treatment was mild, with leukopenia being the treatment-limiting factor. Thrombocyte levels were not altered significantly by treatment. Thus, there seems to be room for dose escalation using granulocyte colony-stimulating factor. There was no considerable cardiotoxicity, central nervous system toxicity, or cystitis observed. The low rate of cardiotoxicity appeared to be related to dose fractionation of epirubicin. After randomization of patients to treatment interruption versus continuation of chemotherapy, a longer relapse-free survival was observed for patients who continued chemotherapy (mean relapse-free survival, 2+ months); however, this did not translate into prolonged survival. The cumulative scores of toxicity and quality of life parameters showed increasing superiority for treatment interruption. Therefore, a strategy of treatment until maximum response and subsequent treatment interruption seems to be superior to treatment continuation.

Antineoplastic Combined Chemotherapy Protocols↗

Devices for blood pressure self measurement: tested in comparison.

OBJECTIVE: Comparative clinical evaluation of instruments designed for the self-measurement of blood pressure. METHOD: The usefulness of 27 different, exclusively oscillometric, automated devices were tested on a single group of 24 test persons without pressure-reducing arterial stenoses in the upper extremity. The cuff was to be put on the upper arm with 20 devices, on the wrist with five devices and on the left index finger with two devices. Per device and test person, six sequential comparative measurements were carried out using automated self-measurement and standard method with a double stethoscope in the same arm. RESULTS: On average, the devices measured the systolic pressure between 13.2 mmHg lower and 3.5 mmHg higher than the standard procedure; the diastolic pressure was measured between 17.4 and 0.2 mmHg lower. Using a scoring system, in which a device only got points for a comparative measurement if the differences to the control in systolic and diastolic measurement both were < or = 10 mmHg, the devices gained between 67 and 259 out of a maximum of 576 points. If each of the test persons had opted to buy just those devices which revealed a mean systolic and diastolic error of < or = 5 mmHg in his or her case, younger test persons would have found zero to five suitable devices older persons three to 13. The site of cuff application had no significant influence on results. CONCLUSIONS: Standard measurements and measurements with automated blood pressure self-measurement devices can differ considerably. In young test persons less suitable instruments are found than for older persons.

Adult↗

Thromboprophylaxis with low-molecular-weight heparin in outpatients with plaster-cast immobilisation of the leg.

Deep-vein thrombosis is common after plaster-cast immobilisation for traumatic injury. We did a randomised prospective study of the effect of low-molecular-weight heparin on the incidence of deep-vein thrombosis in patients with minor injuries treated with plaster-cast immobilisation of the leg. A control group (n = 163) received no prophylaxis, the prophylaxis group received low-molecular-weight heparin once daily (n = 176). The incidence of deep-vein thrombosis in the prophylaxis group was 0% (one tailed p < 0.006) vs 4.3% in the control group. No severe side-effects of low-molecular-weight heparin were observed. Thromboprophylaxis with low-molecular-weight heparin once daily is effective in reducing the risk of deep-vein thrombosis in outpatients with plaster-cast immobilisation of the leg.

Adolescent↗

[ROC analysis in post-processing of image data in digital thoracic radiography].

PURPOSE: To examine the extent to which digital luminescence radiography (DLR) can be used for the imaging of pulmonary nodules and interstitial lung disease in chest radiography without any loss of image quality. Additionally: to examine whether post-processing of image data can optimise the recognizability of varied image details. MATERIALS AND METHODS: Detail perceptibility studies were performed on an anthropomorphic thorax phantom with simulated nodules and small linear and reticular details. Under standard conditions, digital luminescence radiographs were obtained in 7 different image modes, and these were compared with a 200-speed screen-film system. The detection of these systems was evaluated in an ROC analysis on the basis of 19,200 individual observations. RESULTS: Edge enhancement or application of high-frequency-enhancing small filter kernels (S 5) slightly improves the detection of linear structures; however, the illustration of nodular details is markedly reduced. Larger filter kernels (S 20, S 40) make a definitive detection possible--not only of circular, but also of linear details. CONCLUSIONS: Storage phosphor radiographs are equal to the tested analog screen-film-system. The optimization of post-processing can be helpful in the prevention of routine multiple documentations.

Adult↗

[The use of an asymmetric film-screen combination for the imaging of round pulmonary foci].

PURPOSE: To examine the diagnostic advantages of an asymmetric film-screen system (a-FSS) compared to a conventional 200-speed FSS with and without anatomical lung filter. METHODS: Standard radiographs were obtained from an anthropomorphic chest phantom with simulated pulmonary nodules. The existence or non-existence of nodules was assessed in 7344 individual observations. The results were evaluated using ROC analysis. RESULTS: In an overall evaluation the a-FSS with an ROC area of 0.873 +/- 0.018 was not significantly superior (p > 0.05) to the lung filter but significantly superior (p < 0.05) to the 200-speed FSS. In the mediastinum the a-FSS and the lung filter were significantly superior (p < 0.05) to the 200-speed FSS. In the lung areas the 200-speed FSS and the a-FSS attained equivalent results (p > 0.05), whereas the lung filter was rated significantly lower (p < 0.05). CONCLUSIONS: Asymmetric FSS improves chest diagnostics, because it yields significantly more diagnostic information in the mediastinum using equivalent x-ray exposure without reducing the image quality in the lung areas in respect of simulated pulmonary nodules.

Evaluation Studies as Topic↗

Response to methimazole in Graves' disease. The European Multicenter Study Group.

OBJECTIVE: A variety of regimens continue to be used in the treatment of Graves' disease with antithyroid drugs. We have investigated the factors which determine the initial response to methimazole (time until euthyroidism is achieved) in Graves' disease. PATIENTS: Five hundred and nine patients with Graves' disease in different European countries with normal and subnormal iodine supply. Patients were randomized to treatment with either 10 or 40 mg of methimazole per day for one year, with levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months. MEASUREMENTS: Response was assessed by serial measurements of serum thyroid hormones. TSH receptor antibodies, thyroid autoantibodies and urinary iodide excretion were measured centrally. Twenty-minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as well as a stepwise logistic regression model were used to examine the relations between methimazole dose, age, goitre size, presence of endocrine eye signs, thyroid hormone levels, urinary iodide excretion, thyroid uptake, index of disease severity (Crooks), presence of TSH receptor antibodies and duration of the hyperthyroid phase. RESULTS: Within 3 weeks, 40.2% of patients responded to 10 mg of methimazole and 77.5% responded within 6 weeks. The corresponding figures for 40 mg of methimazole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroidism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb), index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed in patients with large goitres, iodine excretion of > or = 100 micrograms/g creatinine, high pretreatment thyroid hormone levels, elevated levels of TBIAb and treatment with only 10 mg of methimazole. In the 10-mg group, 46% of patients were euthyroid within 3 weeks when urinary iodide was < 50 microgram/g of creatinine, and only 27% when iodide was above 100 micrograms/g. By stepwise logistic regression, the main factors for the response to methimazole were daily dose, pretreatment T3 levels, and goitre size. CONCLUSION: Methimazole dose, pretreatment serum T3 levels, and goitre size are the main determinants of the therapeutic response to methimazole in Graves' disease, at least in areas comprising low, subnormal and normal iodine supply.

Adult↗

[ROC analysis of image quality in digital luminescence radiography in comparison with current film-screen systems in mammography].

AIM: To compare in mammography the image quality of digital luminescence radiography (DLR) to that of usual film screen mammography and xeromammography. MATERIALS AND METHODS: Three single emulsion film-screen combinations, one double coated high resolution film and xeroradiography, were tested for this purpose. In our phantom study the detectability of microcalcifications, fibrils and low contrast details were first of all studied separately. Image processing techniques were, for example, contrast variation by grey scale level windowing, "unsharp mask" filtering and regulatable edge enhancement. Phantom images were made and then the image quality was evaluated by observer performance study using a receiver operating characteristic (ROC analysis). RESULTS: Best results in respect of detection of microcalcifications and fibrils were found in xeroradiography, luminescent image plate and double-coated film-screen combination. These systems showed more favourable ROC curves than the single emulsion film-screen combinations. CONCLUSIONS: Our results indicate that image quality of digital images in the field of image processing is equal to that of conventional mammographic techniques and partially superior to detection of low contrast details.

Breast Neoplasms↗

Short-time rabbit model of endotoxin-induced hypercoagulability.

We describe a short-time endotoxin-induced rabbit model of hypercoagulability for the study of the coagulation cascade and the therapeutic effects of coagulation inhibitors. Cardiorespiratory function was maintained in rabbits under general anesthesia and standardized mechanical ventilation (tidal volume, 6 ml/kg; 60 breaths/min) via tracheostomy and low-dose inotropic support. Coagulation parameters such as prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, platelet count, fibrin monomers, D-dimers, antithrombin III and factor XIII activities, thrombelastography, and platelet aggregometry were measured during a 4-h period after sequential double endotoxin administration (80 and 40 micrograms/kg of body weight, intravenously). Mean arterial pressure and arterial and central venous blood gas tensions were monitored. Global clotting, activation parameters of coagulation, and leukocyte count deteriorated significantly in the endotoxin-treated animals but was mainly unaltered in controls (P < 0.05). Tissue specimens of the lungs, liver, brain, and kidneys were examined. Endotoxin-induced, disseminated fibrin deposition was found in the lungs and liver (P < 0.01). We conclude that this short-time model of hypercoagulability in rabbits reliably induced disseminated intravascular coagulation. Tracheostomy and mechanical ventilation provided a reproducible model in which the differences between the controls and the endotoxin-treated animals were exclusively due to administration of endotoxin and not to unforeseen complications of the respiratory system. This model allows the study of therapeutic effects of coagulation inhibitors on endotoxin-induced changes.

Animals↗

ATP-sensitive K+ channels in heart muscle cells first open and subsequently close at maintained anoxia.

In ventricular myocardial cells of the guinea pig and the mouse, anoxia caused after a mean latency of 439 +/- 141 s and 129 +/- 23 s (mean +/- S.E.M.), respectively, a large current through KATP-channels. This current disappeared within several seconds when reoxygenating the cells but decayed also completely at maintained anoxia. The kinetics of the latter process, however, were much slower and obeyed an approximately monoexponential time course with time constants in the range of 30 s. The results suggest that in the ischaemic myocardium KATP-channels contribute only to the initial phase of extracellular K+ accumulation.

Adenosine Triphosphate↗

Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group.

Over the past decade various clinical trials have used monoclonal antibodies as therapeutic agents against solid tumours. No consistent pattern of response or improved survival has yet emerged although antigenic heterogeneity and insufficient accessibility of cells in advanced tumours have been offered as explanations for these failures. We designed a study in which a monoclonal antibody was used to target minimal residual disease in an early stage of tumour cell dissemination in patients with colorectal cancer. Only patients in Dukes' stage C who had undergone curative surgery and were free of manifest residual tumour were admitted. 189 patients with colorectal cancer of stage Dukes' C were randomly assigned to an observation regimen or to postoperative treatment with 500 mg of 17-1A antibody, followed by four 100 mg infusions each month. A balance of risk factors in the two groups was achieved by dynamic randomisation procedure. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% (Cox's proportional hazard, p = 0.04, log-rank p = 0.05) and decreased the recurrence rate by 27% (p = 0.03, p = 0.05). The effect of antibody was most pronounced in patients who had distant metastasis as first sign of a relapse (p = 0.0014, p = 0.002), an effect that was not seen for local relapses (p = 0.74, p = 0.67). Toxic effects of 17-1A antibody were infrequent, consisting mainly of mild constitutional and gastrointestinal symptoms. During 371 infusions four anaphylactic reactions were seen, all controllable by intravenous steroids and none necessitated admission to hospital. Adjuvant therapy with 17-1A antibody extends life and prolongs remission in patients with colorectal cancer of Dukes' stage C.

Antibodies, Monoclonal↗

Anoxia decreases the transient K+ outward current in isolated ventricular heart cells of the mouse.

Transient K+ outward currents (Ito) were measured in enzymatically isolated ventricular mouse heart cells with a patch clamp technique in the whole cell configuration. Exposure of the cells to substrate-free anoxia gradually decreased both the peak and the late Ito. The inactivation time course of Ito was fitted with two exponentials. After 4-10 min of anoxia, the contribution of the fast and slow exponential decreased to 60 +/- 7% and 62 +/- 4% of the control value and recovered after reoxygenation within 1-3 min to 84 +/- 5% and 75 +/- 6% (n = 10; all mean +/- SEM), respectively. The time constants of the exponentials were invariant to anoxia. Voltage dependence of activation and inactivation of Ito were not influenced by anoxia. Application of stimulators of protein kinase A and C, cGMP- dependent protein kinase, or of the oxidant diamide during anoxia did not recover Ito. It is concluded that under conditions of metabolic stress, Ito is reversibly down-regulated leaving inactivation kinetics unchanged. The underlying mechanism is as yet unknown but does neither involve a decreased activity of protein kinase A, protein kinase C, nor c-GMP dependent protein kinase.

Animals↗

[Implementing ambulatory prevention of thrombosis with low molecular weight heparin in plaster immobilization of the lower extremity].

Plaster cast immobilisation following trauma is a major risk factor for the development of deep vein thrombosis. In our controlled, randomized and prospective study in patients with minor injuries the incidence of deep vein thrombosis was 4.3% in conservatively treated outpatients with plaster cast immobilisation of the leg (n = 163 control group without prophylaxis). By application of low molecular weight heparin once daily the number of deep vein thrombosis in the prophylaxis group (n = 176) was reduced to 0% (p = 0.006). No severe side effects of low molecular weight heparin were observed. Subcutaneous injections were self-applicated by 89% of males and 72% of females. We conclude that thromboprophylaxis with low molecular weight heparin once daily is effective to reduce the risk of deep vein thrombosis in outpatients with plaster cast immobilisation of the leg.

Adolescent↗

Preoperative radiochemotherapy and radical surgery in comparison with radical surgery alone. A prospective, multicentric, randomized DOSAK study of advanced squamous cell carcinoma of the oral cavity and the oropharynx (a 3-year follow-up).

A multicentric, randomized study of squamous cell carcinoma (SCC) of the oral cavity and the oropharynx has been undertaken by DOSAK. The results after radical surgery alone have been compared with the results of combined preoperative radiochemotherapy followed by radical surgery. Patients with primary (biopsy proven) SCC of the oral cavity or the oropharynx with tumor nodes metastasis (TNM) stages T2-4, N0-3, M0 were included in the study. A total of 141 patients were treated by radical surgery alone, whereas 127 patients were treated by radical surgery preceded by preoperative radiochemotherapy. The preoperative treatment consisted of conventionally fractioned irradiation on the primary and the regional lymph nodes with a total dose of 36 Gy (5 x 2 Gy per week) and low-dose cisplatin chemotherapy with 5 x 12.5 mg cisplatin per m2 of body surface during the first week of treatment. Radical surgery according to the DOSAK definitions (DOSAK, 1982) was performed after a delay of 10-14 days. During the follow-up period, 28.2% of all patients suffered from locoregional recurrence, and 27.2% of the patients died. The percentages were higher after radical surgery alone for locoregional recurrence (31% and 15.6%) and for death (28% and 18.6%). The life-table analysis showed improved survival rates of 4.5% after 1 year and 8.3% after 2 years in the group of patients treated with combined therapy. The demonstrated improvement appeared to be significant with the Gehan-Wilcoxon test as well as with the log rank test below a P value of 5%.

Carcinoma, Squamous Cell↗

[Are high-intensifying film-screen combinations suitable for the detection of fine interstitial lung changes? The results of a ROC study with an anthropomorphic thorax phantom].

Exposures of an anthropomorphic thorax phantom in posteroanterior projection were made using a focus-film distance of 200 cm and 125 kV with film-screen combinations in class 200 (Curix RP 1L/MR 200) and class 400 (Curix ST-L/Regular). Pathomorphological structures of the lung parenchyma of fine nodular, linear and reticular types were simulated by suitable materials. A ROC analysis including a t-test showed no significant difference in the evaluation of these structural details (p > 0.05). In order to describe image quality for the two film-screen systems, density curves, sigma D-curves and modulation transfer function (MTF) were determined. The only demonstrable difference was reduced MTF of 10-15% for the higher intensification film-screen combination with a resulting poorer resolution of 3.7 l/mm (for the 400 system) compared with 4.3 l/mm for the 200 system.

Evaluation Studies as Topic↗