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Biomedical subjects

M Schumacher

Publications and source records attributed to M Schumacher.

At least 19 recordsLinked to original sources

High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: first results of a randomized trial.

PURPOSE: Investigation of high-dose chemotherapy (HD-CT) followed by autologous hematopoietic stem-cell support compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more positive axillary lymph nodes. PATIENTS AND METHODS: Between November 1993 and September 2000, 307 patients were randomized to receive (following four cycles of epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), intravenously every 21 days) either HD-CT of cyclophosphamide 1500 mg/m(2), thiotepa 150 mg/m(2), and mitoxantrone 10 mg/m(2), intravenously for 4 consecutive days followed by stem-cell support; or SD-CT in three cycles of cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) intravenously on days 1 and 8, every 28 days. The primary end point was event-free survival. RESULTS: After a median follow-up of 3.8 years, 144 events with respect to event-free survival have been observed (HD-CT: 63 events; SD-CT: 81 events). The first event of failure (HD-CT v SD-CT) was an isolated locoregional recurrence (nine v 11), a distant failure (52 v 68), and death without recurrence (two v two). The estimated relative risk of HD-CT versus SD-CT was 0.75 (95% CI, 0.54 to 1.06; P =.095). Overall survival showed no difference (HD-CT: 40 deaths; SD-CT: 49 deaths). CONCLUSION: There was a trend in favor of HD-CT with respect to event-free survival, but without statistical significance. Further follow-up and a meta-analysis of all randomized studies will reveal the effect of HD-CT as compared with SD-CT as adjuvant treatment in high-risk primary breast cancer.

Adult↗

Parkes Weber or Klippel-Trenaunay syndrome? Non-invasive diagnosis with MR projection angiography.

Klippel-Trenaunay and Parkes Weber (Klippel-Trenaunay-Weber) syndromes consist of vascular malformations of the capillary, venous and lymphatic systems combined with soft tissue and bone hypertrophy of the affected extremity. Klippel-Trenaunay syndrome is a pure low-flow condition, while Parkes Weber syndrome is characterized by significant arteriovenous fistulas. The distinction of both entities is relevant, since the prognosis and therapeutic strategies differ significantly. Our purpose is to demonstrate that thick-slice dynamic magnetic resonance projection angiography (MRPA) is a non-invasive tool to detect arteriovenous shunting in Parkes Weber syndrome. Four patients underwent MR imaging and MRPA. MRPA demonstrated arteriovenous shunting in three patients. Arteriovenous shunting was characterized by early appearing draining veins. The time of arrival between normal arteries and pathological veins varied between less than 0.5 and 1.0 s. Therefore, the diagnosis in these cases could be specified as Parkes Weber syndrome. In all these cases, arteriovenous shunting was confirmed by intraarterial digital subtraction angiography. One patient showed normal results in MRPA and could be diagnosed as having Klippel-Trenaunay syndrome.

Adult↗

Radiation therapy after breast-conserving surgery; first results of a randomised clinical trial in patients with low risk of recurrence.

To study the role of radiotherapy and tamoxifen after breast-conserving surgery (BCS) in patients with a favourable prognosis, a clinical trial was initiated by the German Breast Cancer Study Group. Between 1991 and 1998, 361 patients (pT1pN0M0, aged 45-75 years, receptor positive, grade I-II) were randomised to radiotherapy (yes/no) and tamoxifen for 2 years (yes/no) in a 2x2 factorial design; the exclusion of seven centres (14 patients) left 347 patients in the analysis. After a median follow-up of 5.9 years, 77 events concerning event-free survival have been observed. Since a strong interactive effect between radiotherapy and tamoxifen has been established, the results are presented in terms of the treatment effects for all four treatment groups separately. Mainly due to the presence of local recurrences, the event rate was about three times higher in the group with BCS only than in the other three groups. No difference could be established between the four treatment groups for distant disease-free survival rates. It is concluded that even in patients with a favourable prognosis, the avoidance of radiotherapy and tamoxifen after BCS increases the rate of local recurrences substantially.

Aged↗

Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord.

Progesterone (PROG) provides neuroprotection to the injured central and peripheral nervous system. These effects may be due to regulation of myelin synthesis in glial cells and also to direct actions on neuronal function. Recent studies point to neurotrophins as possible mediators of hormone action. Here, we show that the expression of brain-derived neurotrophic factor (BDNF) at both the mRNA and protein levels was increased by PROG treatment in ventral horn motoneurons from rats with spinal cord injury (SCI). Semiquantitative in situ hybridization revealed that SCI reduced BDNF mRNA levels by 50% in spinal motoneurons (control: 53.5+/-7.5 grains/mm(2) vs. SCI: 27.5+/-1.2, P<0.05), while PROG administration to injured rats (4 mg/kg/day during 3 days, s.c.) elicited a three-fold increase in grain density (SCI+PROG: 77.8+/-8.3 grains/mm(2), P<0.001 vs. SCI). In addition, PROG enhanced BDNF immunoreactivity in motoneurons of the lesioned spinal cord. Analysis of the frequency distribution of immunoreactive densities (chi(2): 812.73, P<0.0001) showed that 70% of SCI+PROG motoneurons scored as dark stained whereas only 6% of neurons in the SCI group belonged to this density score category (P<0.001). PROG also prevented the lesion-induced chromatolytic degeneration of spinal cord motoneurons as determined by Nissl staining. In the normal intact spinal cord, PROG significantly increased BDNF inmunoreactivity in ventral horn neurons, without changes in mRNA levels. Our findings suggest that PROG enhancement of endogenous neuronal BDNF could provide a trophic environment within the lesioned spinal cord and might be part of the PROG activated-pathways to provide neuroprotection.

Animals↗

Systemic progesterone administration results in a partial reversal of the age-associated decline in CNS remyelination following toxin-induced demyelination in male rats.

In order to establish the effects of systemically administered progesterone on central nervous system (CNS) remyelination, a toxin-induced model of CNS demyelination was used in which the rate of remyelination is age-dependent. The rapid remyelination in young adult rats allowed an assessment of potential adverse effects of progesterone while the slow remyelination in older adult rats allowed an assessment of its potentially beneficial effects. There was no significant difference in the rate of remyelination between young control and treated animals. However, a modest but significant increase in the extent of oligodendrocyte remyelination in response to progesterone (and a comparable significant decrease in the proportion of axons that remained demyelinated) was observed in older rats 5 weeks after lesion induction. We also found a significant increase in the proportion of Schwann cell remyelinated axons between 3 and 5 weeks after lesion induction that was not apparent in the control animals. These results indicate that progesterone does not inhibit CNS remyelination and that it has a positive modulating effect on oligodendrocyte remyelination in circumstances where it is occurring sub-optimally.

Aging↗

Does the architecture of hospital facilities influence nosocomial infection rates? A systematic review.

OBJECTIVE: To review the evidence regarding the effects of interventions to improve hospital design and construction on the occurrence of nosocomial infections. METHODS: Systematic review of experimental and non-experimental, architectural intervention studies in intensive care units (ICUs), surgical departments, isolation units, and hospitals in general. The studies dated from 1975, and were in English, French, German, Italian, and Spanish. Regardless of format, the studies were identified through seven medical databases, reference lists, and expert consultation. RESULTS: One hundred seventy-eight scientific articles were identified; however, none of these described a meta-analysis, systematic review, or randomized, controlled trial. Most of the articles were categorized at the lowest level of evidence (expert judgment or consensus statements). Only 17 described completed concurrent or historical cohort studies matching the inclusion criteria (ICUs, 9; surgical departments, 4; isolation units, 2; hospitals in general, 2). The interventions generally included a move to other premises or renovation. However, in many studies, the staff-to-patient ratio was also improved. Some studies showed lower infection rates after intervention, but this finding cannot be generalized because of confounding and frequently small study populations. CONCLUSIONS: The lack of stringent evidence linking hospital design and construction with the prevention of nosocomial infection is partly attributable to the multifactorial nature of these infections, and some improvement will be seen if basic conditions such as the availability of sufficient space, isolation capacity, and facilities for handwashing are met. However, to our knowledge, other factors, especially the improper hand hygiene of medical staff, have greater impact.

Architecture↗

Long- and medium-term ozone effects on lung growth including a broad spectrum of exposure.

The effects of semi-annual and 3.5 yr mean ozone (O3) concentrations on children's forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were assessed over a study period of 3.5 yrs in 2,153 schoolchildren from 15 study sites in South Western Germany and Lower Austria. Spirometric parameters were assessed twice a year, and differences between consecutive measurements divided by days were considered as a measure of lung growth. Exposure was analysed in four classes, separately for winter and summer (semi-annual mean O3 concentrations 22-30, 30-38, 38-46, 46-54 parts per billion (ppb) in summer and 4-12, 12-20, 20-28, 28-36 ppb in winter). Regression methods for repeated measurements were used, and these revealed a significantly lower FVC (FEV1) increase estimated at -19.2 (-18.5) mL x 100 days(-1) for semi-annual mean O3 exposure in summer between 46 and 54 ppb compared to exposure between 22 and 30 ppb. However, in winter, the estimated difference in FVC (FEV1) was 16.4 (10.9) mL x 100 days(-1) between the semi-annual O3 class 28-36 ppb and the 4-12 ppb class. By means of linear regression the study found that there was no association between growth rates and mean summer O3 for FVC and FEV1 over a 3.5 yr period. The authors conclude that medium-term effects on schoolchildren's lung growth are possibly present, but are in the long-term not detectable for forced vital capacity and forced expiratory volume in one second over a 3.5 yr period due to partial reversibility.

Air Pollutants↗

Quality of life in goserelin-treated versus cyclophosphamide + methotrexate + fluorouracil-treated premenopausal and perimenopausal patients with node-positive, early breast cancer: the Zoladex Early Breast Cancer Research Association Trialists Group.

PURPOSE: To compare quality of life (QoL) in premenopausal and perimenopausal patients with node-positive, early breast cancer treated with the endocrine agent goserelin (Zoladex; AstraZeneca Pharmaceuticals LP, Wilmington, DE) or cyclophosphamide + methotrexate + fluorouracil (CMF). PATIENTS AND METHODS: Patients from 86 centers worldwide were randomly assigned to receive either goserelin (3.6 mg every 28 days for 2 years; n = 514) or CMF (six 28-day cycles; n = 496), and were included in the QoL study. QoL was assessed using a self-administered patient questionnaire that consisted of 39 items from the Rotterdam Symptom Checklist, including dimensions evaluating physical and psychological symptom distress, activities of daily living, hormonal effects, and an assessment of overall QoL. RESULTS: Early benefits were noted during months 3 to 6 of treatment, for goserelin compared with CMF. Significant differences were found for changes in overall QoL (eg, 6.96 +/- 0.88 v 0.69 +/- 0.92 at 6 months; P <.0001) and for physical symptom distress, activity levels, and "effort to cope with illness" dimensions. At 1, 2, and 3 years, there were no significant differences in overall QoL or specific QoL dimensions. Scores for hormonal symptoms were worse with goserelin during the 2-year goserelin treatment period; however, this trend was reversed at 3 years. CONCLUSION: Goserelin offers improved overall QoL during the first 6 months of therapy compared with CMF chemotherapy in premenopausal and perimenopausal patients with early breast cancer. Coupled with equivalent efficacy in estrogen receptor-positive patients, these data support the use of goserelin as an alternative to CMF in premenopausal and perimenopausal patients with estrogen receptor-positive, node-positive early breast cancer.

Adult↗

First Measurement of the Gerasimov-Drell-Hearn Sum Rule for 1H from 0.7 to 1.8 GeV at ELSA.

To verify the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the first time experimentally, we measured the helicity dependent total photoabsorption cross section with circularly polarized real photons and longitudinally polarized nucleons in the photon energy range 0.68-1.82 GeV with the tagged photon facility at ELSA. The experiment was carried out with a 4pi detection system, a circularly polarized tagged photon beam, and a frozen spin polarized proton target. The contribution to the GDH sum rule in this photon energy range is [49.9+/-2.4(stat)+/-2.2(syst)] microb.

Journal Article↗

Cerebral arteriovenous malformations: influence of angioarchitecture on bleeding risk.

BACKGROUND: To evaluate the angioarchitecture of cerebral arteriovenous malformations (cAVMs) with special regard to its influence on the risk of intracranial haemorrhage. METHODS: Clinical and neuroradiological data of 171 patients with cAVMs, who were treated at our department, were analysed retrospectively. The angioarchitectonic data were obtained from angiographic series, cranial CT scans and MR images. A chi(2) test was conducted to correlate the parameters and determine the P values. FINDINGS: The following parameters correlate to an increased risk of haemorrhage: diameter of the nidus < or =2 cm (P<0.001), number of arterial feeders < or =2 (P<0.001), diameter of the main feeder < or =1 mm (P<0.0001), number of veins draining the nidus < or =2 (P<0.001), exclusive deep drainage (P<0.05), and low or middle flow-velocity (P<0.01). Specific angioarchitectonic features such as venous stenoses, varicose dilatation of the draining vein, arterial aneurysms of the feeding artery, arteriovenous fistula within the nidus, contralateral drainage and sinushypo/-aplasia did not alter the bleeding rate. INTERPRETATION: Various angiographic features were correlated with the occurrence of intracranial haemorrhage in patients with cerebral AVMs. In addition to the well-known factors influencing the bleeding risk of cAVMs like size, pattern of venous drainage and location within the brain our data demonstrate the importance to look at the diameter of the main feeder and the number of draining veins showing a better correlation.

Adolescent↗

Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF).

The purpose of this study was to compare changes in bone mineral density (BMD) in premenopausal patients with node-positive early breast cancer treated with goserelin (Zoladex) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients ( n=1640) were randomized to goserelin (3.6 mg every 28 days for 2 years) or CMF (sixx28-day cycles) treatment. In a protocoled sub-study involving 96 patients from eight centers (goserelin: n=53; CMF: n=43), lumbar spine (L2-L4) and femoral neck BMD were assessed by dual X-ray absorptiometry at baseline and then annually for 3 years. At the end of the 2-year goserelin-treatment period, mean BMD losses for goserelin-treated and CMF-treated patients were -10.5% and -6.5% ( P=0.0005) for lumbar spine and -6.4% and -4.5% ( P=0.04) for femoral neck, respectively. At 3 years, partial recovery of BMD was observed in goserelin recipients. In contrast, mean BMD losses for the CMF group indicated persistent BMD loss. No significant differences in BMD were observed between groups at the 3-year assessment of the spine or femoral neck. In the CMF group, based on amenorrhea status at 48 weeks, BMD losses at the lumbar spine were greater for amenorrheic than non-amenorrheic patients. Ovarian suppression resulting in amenorrhea was closely related to BMD loss in both treatment groups. Overall, patients who received CMF did not show recovery of BMD throughout follow-up, whereas partial recovery was observed 1 year after cessation of goserelin therapy, associated with the return of ovarian function in the majority of patients.

Adult↗

Head and neck vascular malformations: time-resolved MR projection angiography.

Extracranial vascular anomalies can be divided into haemangiomas and vascular malformations. The latter can be subdivided on the basis of the predominant type of vascular channels. Separation of high- and low-flow vascular malformations is of clinical importance. We report preliminary observations on time-resolved magnetic resonance projection angiography (MRPA) of vascular malformations of the head and neck. We examined eight patients with vascular anomalies of the head and neck. On MRPA the time between the early arterial phase and enhancement of the malformation could be used to distinguish high- and low-flow lesions. High-flow arteriovenous malformations showed early, intense enhancement. Venous malformations were either not visible on MRPA or showed late enhancement of veins. One patient was examined after embolisation of an arteriovenous fistula of the mandible. Normal MRPA was taken to indicate absence of a residual lesion.

Adolescent↗

Mifepristone (RU486) protects Purkinje cells from cell death in organotypic slice cultures of postnatal rat and mouse cerebellum.

Mifepristone (RU486), which binds with high affinity to both progesterone and glucocorticosteroid receptors (PR and GR), is well known for its use in the termination of unwanted pregnancy, but other activities including neuroprotection have been suggested. Cerebellar organotypic cultures from 3 to 7 postnatal day rat (P3-P7) were studied to examine the neuroprotective potential of RU486. In such cultures, Purkinje cells enter a process of apoptosis with a maximum at P3. This study shows that RU486 (20 microM) can protect Purkinje cells from this apoptotic process. The neuroprotective effect did involve neither PR nor GR, because it could not be mimicked or inhibited by other ligands of these receptors, and because it still took place in PR mutant (PR-KO) mice and in brain-specific GR mutant mice (GRNes/Cre). Potent antioxidant agents did not prevent Purkinje cells from this developmental cell death. The neuroprotective effect of RU486 could also be observed in pathological Purkinje cell death. Indeed, this steroid is able to prevent Purkinje cells from death in organotypic cultures of cerebellar slices from Purkinje cell degeneration (pcd) mutant mice, a murine model of hereditary neurodegenerative ataxia. In P0 cerebellar slices treated with RU486 for 6 days and further kept in culture up to 21 days, the synthetic steroid increased by 16.2-fold the survival of pcd/pcd Purkinje cells. Our results show that RU486 may act through a new mechanism, not yet elucidated, to protect Purkinje cells from death.

Animals↗

Compton scattering from the deuteron and extracted neutron polarizabilities.

Differential cross sections for Compton scattering from the deuteron were measured at MAX-Lab for incident photon energies of 55 and 66 MeV at nominal laboratory angles of 45 degrees, 125 degrees, and 135 degrees. Tagged photons were scattered from liquid deuterium and detected in three NaI spectrometers. By comparing the data with theoretical calculations in the framework of a one-boson-exchange potential model, the sum and the difference of the isospin-averaged nucleon polarizabilities, alpha(N)+beta(N)=17.4+/-3.7 and alpha(N)-beta(N)=6.4+/-2.4 (in units of 10(-4) fm(3)), have been determined. By combining the latter with the global-averaged value for alpha(p)-beta(p) and using the predictions of the Baldin sum rule for the sum of the nucleon polarizabilities, we have obtained values for the neutron electric and magnetic polarizabilities of alpha(n)=8.8+/-2.4(total)+/-3.0(model) and beta(n)=6.5-/+2.4(total)-/+3.0(model), respectively.

Journal Article↗

Activated clotting time or activated partial thromboplastin time as the method of choice for patients undergoing neuroradiological intervention.

We evaluated the role of the activated clotting time (ACT) and activated partial thromboplastin time (APTT), both currently available as bedside tests, for monitoring anticoagulation following bolus injection of 2500 or 5000 IU heparin in 21 patients undergoing neuroradiological procedures. APTT was measured using the CoaguChek Pro device compared to the laboratory standard measurement and ACT comparing CoaguChek Pro to Hemochron Celite and Kaolin. Statistical analysis was performed using Bablok-Passing regression. Despite heparin doses of 2500-5000 IU APTT measurements were out of range in 67% of patients using CoaguChek Pro and in 76.5% of patients using the laboratory measurement. ACT was reliably determined in all patients. The correlation between the different devices (CoaguChek Pro vs. Hemochron Celite r=0.69, Kaolin r=0.78) and assays (Hemochron Celite/Kaolin r=0.85) was good. ACT ranged from 141-417 s measured by CoaguChek Pro and 138-320 s measured by Hemochron Celite and 172-381 s using Hemochron Kaolin. These results indicate that ACT is the method of choice for monitoring anticoagulation in neuroangiographic procedures.

Female↗

The balloon retriever technique.

We report a 50-year-old woman with a large supraophthalmic aneurysm. An attempt was made to treat this by endovascular occlusion of the distal internal carotid artery with coils but they could not be placed satisfactorily. During withdrawal a coil became stuck, stretched and finally detached inside the guiding catheter. It was salvaged easily with a balloon retriever technique. This seems to be a useful way to remove stretched coils.

Carotid Artery, Internal↗

Subarachnoid haemorrhage due to cervical spinal cord haemangioblastomas in a patient with von Hippel-Lindau disease.

A case is presented with severe infra- and supratentorial subarachnoid haemorrhage (SAH) caused by intramedullary haemangioblastomas of the cervical spinal cord. The patient initially had a typical SAH symptomatology without neurological deficit. The cerebral angiogram was nondiagnostic. After admission the patient developed slightly progressive right sensorimotor paresis. Angiography of the cervical spine and MRI delineated three intramedullary haemangioblastomas. Retrospectively the diagnosis of von Hippel-Lindau (VHL) disease was made by multiple haemangioblastomas and a positive family history. The three lesions were surgically completely removed.

Cervical Vertebrae↗