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Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 37 records · Page 2Linked to original sources

Vascular endothelial growth factor in pleural effusions of different origin.

This study aimed to determine the diagnostic relevance of vascular endothelial growth factor (VEGF) in the pleural fluid and serum of patients with pleural effusions of different aetiology. VEGF was quantified in the pleural effusion fluid and serum of 96 patients with malignancies (58 lung cancers (CA) and 38 tumours with secondaries to the lung (TM)), 45 with congestive heart failure (CHF), 28 with tuberculosis (TB), 45 with acute infections (INF), and in the serum of 20 healthy controls. VEGF pleural effusion concentrations were significantly different in the main diagnostic groups. VEGF was higher in effusions of patients with malignancies (CA as well as TM) in comparison with INF, TB or CHF. In serum, however, high VEGF concentrations indicated CA, TM or INF, but not TB or CHF. Despite significant differences of VEGF levels in different patient groups, receiver-operating characteristic analysis revealed insufficient diagnostic value of VEGF for differential diagnosis of pleural effusions. In conclusion, vascular endothelial growth factor serum concentration is highly suggestive of the presence of lung disease in general, except for tuberculosis. In effusion fluid, the presence of vascular endothelial growth factor clearly indicates inflammatory or malignant origin. However, for diagnostic use, additional parameters besides vascular endothelial growth factor are mandatory.

Adult↗

High bone-binding capacity of ibandronate in hemodialysis patients.

Bisphosphonates are a potential therapy for osteoclast-mediated bone disease, such as renal osteodystrophy. This study evaluated ibandronate bone-binding in patients with secondary hyperparathyroidism and renal osteodystrophy and examined whether there is a correlation with bone metabolism parameters. Sixteen patients with end-stage renal disease and secondary hyperparathyroidism receiving regular hemodialysis were recruited to this 12-week trial. Intravenous ibandronate 2 mg was administered for 5 min every 4 weeks directly after hemodialysis. Ibandronate levels were measured 15 min after infusion and at trough levels before the next hemodialysis. Serological markers of bone metabolism were also measured. After the first infusion, the peak ibandronate level was 154 +/- 75.1 ng/ml and the trough level was 2.7 +/- 1.7 ng/ml. At week 12, peak and trough ibandronate levels were 164.8 +/- 89.9 ng/ml and 3.2 +/- 2.6 ng/ml, respectively. Ibandronate bone uptake was 98.0% at first application and 98.4% at week 12. In patients with remaining diuresis, ibandronate urine excretion was < 0.001% of the administered dose. There was no correlation of ibandronate bone-binding with parameters of osteoclast activity or parathyroid hormone (PTH). The correlation with markers of osteoblast activity was significant but weak. Ibandronate had a bone-binding capacity of approximately 98% in hemodialysis patients. After repeated dosing ibandronate bone-uptake remained stable and was independent of osteoclast activity or PTH levels. Due to the high bone-binding of ibandronate in these patients, a 2 mg dose of intravenous ibandronate is equivalent to a 4-5 mg dose of ibandronate in patients with normal renal function.

Adult↗

Functional role of TRPC proteins in vivo: lessons from TRPC-deficient mouse models.

In order to elucidate the functional role of TRPC genes, in vivo, the targeted inactivation of these genes in mice is an invaluable technique. In this review, we summarize the currently available results on the phenotype of TRPC-deficient mouse lines. The analysis of mice with targeted deletion in three TRPC genes demonstrates that these proteins represent essential constituents of agonist-activated and phospholipase C-dependent Ca2+ entry channels in primary cells. Furthermore, from the deficits observed in these TRPC-deficient mouse lines a striking number of biological functions could already be ascribed to TRPC2, TRPC4, and TRPC6, not only on the cellular level but also for complex organ functions and integrative physiology. Accordingly, TRPC2 proteins are critically involved in pheromone sensing by neurones of the vomeronasal organ and, thereby, in the regulation of sexual and social behavior of mice, TRPC4 proteins are essential determinants of endothelial-dependent regulation of vascular tone, endothelial permeability, and neurotransmitter release from thalamic interneurones, and TRPC6 proteins are supposed to have a fundamental role in the regulation of smooth muscle tone in blood vessels and lung.

Animals↗

New nomogram for foetal weight estimation based on Hadlock's two-parameter formula.

AIM: To develop and validate a graphical method for ultrasonic foetal weight estimation with predictive qualities comparable to state-of-the-art computational methods. METHOD: Study data were obtained from 3839 consecutive singleton pregnancies with ultrasound examination within 7 days of delivery. We translated the well established Hadlock 2-parameter formula based on abdomen circumference and femur length into a nomogram [corrected]. We compared the measured foetal weight with estimations obtained from this new nomogram and three other methods. RESULTS: Measured by the foetal weight percentage error the new nomogram underestimates the foetal weight on average by 2.5 % (9.86) (mean [SD]) with uniform results over the complete birth weight spectrum. By the same measurement the Hadlock 4-parameter formula underestimates the foetal weight by 1.2 % (9.3) whereas the Hansmann nomogram overestimates the foetal weight by 14.5 % (16.1) The difference between the estimated foetal weight percentage error obtained from the new nomogram and from the Hadlock 2-parameter formula is 0.06 % (0.27) and hence clinically irrelevant. CONCLUSION: The new nomogram has predictive qualities comparable to state-of-the-art computational methods and is thus not only as reliable but also easy to use in situations when computers are not available. It can be recommended for foetal weight estimation over the whole spectrum of birth weight.

Embryonic and Fetal Development↗

Chemotherapy with cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone (CHOEP) is not effective in patients with enteropathy-type intestinal T-cell lymphoma.

BACKGROUND: Enteropathy-type intestinal T-cell lymphoma (ETCL) is a highly aggressive disease with poor response to conventional CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. According to promising data with the addition of etoposide (E) to the CHOP regimen (CHOEP) in aggressive lymphomas including T-cell lymphomas, we have treated patients with ETCL with CHOEP chemotherapy. PATIENTS AND METHODS: Ten consecutive patients (six female, four male) suffering from ETCL were given CHOEP at our institution. Four patients had advanced disease (stage III/IV), while five patients were rated to be in stage II and one in stage I. Treatment consisted of doxorubicin 50 mg/m2, cyclophosphamide 750 mg/m2 and vincristine 1.4 mg/m2 by intravenous infusion on day 1, etoposide 100 mg/m2 intravenously days 1-3 and oral prednisone days 1-5. Cycles were repeated every 3 weeks for a maximum of six courses. Assessment of response was done by means of conventional computed tomography scanning, endoscopy and also [18F]fluorodeoxyglucose positron emission tomography (FDG PET) in seven patients. RESULTS: A total of 41 cycles (median six, range one to six) were administered to our patients. Leukocytopenia/neutropenia WHO grade IV necessitating granulocyte colony-stimulating factor support occurred in all patients evaluable for toxicity, and febrile neutropenia was seen in two patients. Two patients had to undergo emergency surgery due to intestinal perforation after one and three courses of treatment, respectively. Therapeutic results, however, were disappointing: two patients had complete remission (CR), three had partial remissions and five patients progressed during treatment. Remissions, however, where only short-lasting, as only two patients are alive at a median follow-up of 7 months (range 2-16). One patient is in ongoing CR 10 months after initiation of chemotherapy and the other is currently undergoing second-line treatment for progressive disease as judged by follow-up investigations after three cycles of CHOEP. CONCLUSIONS: Our data demonstrate that CHOEP chemotherapy results in a high rate of hematotoxicity in patients with ETCL. In spite of this, therapeutic results were disappointing and do not appear to be superior to conventional CHOP chemotherapy. We conclude that CHOEP cannot be recommended for routine use in patients with ETCL.

Administration, Oral↗

Therapy of IgA nephropathy with mycophenolate mofetil--report of 3 cases.

Mycophenolate mofetil is an immunosuppressive agent in transplantation which inhibits the purin neogenesis. Proliferating lymphocytes are suppressed and antibody production is decreased. Many cases of successful therapy in different kidney diseases are reported, such as diffuse proliferative lupus nephritis, pauci-immune necrotizing glomerulonephritis, focal segmental glomerular sclerosis and IgA nephropathy. We report 3 patients with IgA nephropathy who were treated with mycophenolate mofetil for more than 1 year. In all patients, proteinuria decreased significantly and the renal function remained stable. In 2 patients, kidney biopsy was repeated after 12 months and 18 months, respectively. There were no histological signs of progression of the disease. Two patients developed infections during treatment. One patient had a pneumonia, and a second patient an infection with varizella zoster. Based on our data, mycophenolate mofetil can be a potential treatment of IgA nephropathy. Further controlled studys are warranted to investigate the role of mycophenolate mofetil in IgA nephropathy.

Adult↗

Sleep apnea and hypertension.

Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing and frequently coexists with obesity. Almost 15 million Americans are affected by this disorder. This prevalence is likely increasing, given the current epidemic of obesity. Recent data confirm an association between sleep apnea and several cardiovascular disease conditions, suggesting that OSA may be a new risk factor for coronary artery disease, heart failure, heart rhythm disturbances and hypertension, independent of body mass index. In this review, the authors focus on the nature of the association between OSA and hypertension, the evidence suggesting a causal interaction, and discuss the potential pathophysiologic mechanisms responsible. These mechanisms include activation of the sympathetic and renin-angiotensin-aldosterone systems (RAAS), oxidative stress, and systemic and vascular inflammation, all of which could link OSA to a sustained increase in blood pressure. The authors also review potential therapeutic strategies for the hypertensive patient with OSA.

Humans↗

[Acute renal failure and 2,8-dihydroxyadeninuria].

We report the case of a 65 year old man, with a history of recurrent urolithiasis, who was referred for an acute renal failure. Investigations deny obstructive or glomerular involvement. 2,8-Dihydroxyadeninuria was diagnosed with the help of crystalluria. This rare metabolic disease is due to a deficiency of adenine phosphoribosyltransferase, a purine salvage enzyme. Allopurinol, a low purine diet and high fluid intake made possible the nearly entire regression of renal failure.

Acute Kidney Injury↗

Emotional stroke: clinicoradiologic profile.

OBJECTIVE: Relationships of emotional stressors (ES), stroke subtypes, and mechanisms. METHODS: Stroke risk factors (RF) (n = 26), personal/emotional stressors (ES), and life change units (Holmes and Rahe scale) were evaluated. RESULTS: Of patients with cerebral infarct (n = 1000), 36 (3.6%) had significant ES. Infarct topography involving partial anterior circulation (PAC) (n = 18; 50%) was most frequent. Etiologies (TOAST classification) of small vessel (n = 11; 31%), "other" (coagulopathy, vasculopathy) (n = 8; 22%), and unknown (n = 5; 14%) (P = 0.05). Cognitive impairment was seen most frequently in the ES group (28/36; 78% versus 606/1000; 61%; P = 0.03). Neurologic deficit by Canadian Neurologic Scale (mean 10.3, range 11.5-4.5) was mild. Disability (Rankin scale) was minimal: mild grade 0-2 (n = 30/36; 83%), moderate grade 3-4 (n = 4/36; 11%) (P = 0.0001). MRI showed that subcortical lesion topography (n = 23/36; 64%) predominated over cortical lesions (n = 13/36; 36% P = 0.05). CONCLUSIONS: With ES and stroke, partial anterior circulation stroke and subcortical lesions are significant, unknown and other causes are most frequent, deficit and handicap are mild, but neurocognitive deficit is frequent.

Adult↗

Gamma-irradiation of blood products following autologous stem cell transplantation: surveillance of the policy of 35 centers.

Blood products should be irradiated during allogeneic stem cell transplantation and before performing autologous stem cell harvest for prevention of acute transfusion-associated graft-versus-host disease (TA-GVHD). Usually, irradiation of all blood products is continued lifelong in the allogeneic setting. Up to now, no broadly accepted rules exist concerning autologous stem cell transplantation. We present here the results of an inquiry sent to 47 German transplantation centers regarding the transfusion policy following autologous stem cell transplantation. The results of 35 answering centers are included. Ten out of 35 centers offer irradiated blood products lifelong to their patients, mainly for the prevention of mistransfusion of non-irradiated blood components to allogeneic recipients. Twenty-two out of 35 centers administer irradiated blood products for a special time span after autologous stem cell transplantation. In most centers, this time span is from 3 to 6 months. Only few centers (4/35) expand this time span to 1-2 years after transplantation. A minority of centers (3/35) gave non-irradiated blood products to all of their patients or to patients not suffering from acute leukemia or after total body irradiation (TBI) containing preparative regimens. Most centers (19/35) deliver irradiated blood products irrespective of the conditioning regimen. Fifty-three percent of the centers decide to donate irradiated blood products not depending on immunological reconstitution. But in most centers some kind of hematological reconstitution is a major criterion for termination of irradiated blood products. Sixty-four percent of the centers made no difference in transfusion policy in regard to the underlying disease. No center experienced cases of proofed TA-GVHD. Guidelines should be worked out concerning transfusion policy after autologous stem cell transplantation.

Blood↗

Impact of growth hormone on central nervous activity, vigilance, and tiredness after short-term therapy in growth hormone-deficient adults.

Impairment of well-being and cognitive function has been reported in growth hormone-deficient adults, as well as an improvement of these parameters after GH substitution, albeit inconsistently. The effect of growth hormone on central nervous activity, vigilance and sleepiness was studied prospectively in 16 growth hormone-deficient adults (7 females, 9 males, mean age: 36.8 yrs) with multiple pituitary hormone deficiencies before and 3 months after the start of growth hormone substitution using two objective methods of measurement, pupillographic sleepiness test and a choice reaction time test. Significant differences were found for neither pupillary unrest index nor for reaction time, false or missing reactions in 12 evaluable patients (7 females, 5 males, mean age 37.8 years). Because of the known interrelationships between growth hormone, sleep and mood, the visual analogue scale for tiredness and standardized retrospective questionnaires regarding sleep and mood (Pittsburgh sleep quality index, Epworth sleepiness scale, Depression scale) were used as additional methods. After GH substitution, there was no difference in sleep efficiency and daytime sleepiness, but some of the subjective sleep parameters (sleep quality and sleep latency) improved significantly. There was a tendency for mood improvement, too. Although results must be interpreted cautiously due to the small sample size, we conclude that the improved sleep and mood parameters might be caused by other indices of general well-being in our study.

Adaptation, Ocular↗

18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for assessment of enteropathy-type T cell lymphoma.

BACKGROUND AND AIMS: Enteropathy-type T cell lymphoma (ETCL) represents a relatively rare disease, accounting for less than 1% of non-Hodgkin's lymphomas. ETCL is an aggressive lymphoma which may either present de novo or arise in the context of longstanding or untreated coeliac disease (CD). The aim of this study was to evaluate the potential of 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for imaging of ETCL. Furthermore, we wished to evaluate whether the presence of CD might provide a potential diagnostic obstacle to imaging of lymphoma due to unspecific 18F-FDG uptake and whether accumulation of 18F-FDG within the gut correlates with activity of CD. PATIENTS AND METHODS: We retrospectively analysed patients with ETCL and individuals suffering from CD undergoing 18F-FDG-imaging at our PET unit. Material for histological reassessment by a reference pathologist had to be available for inclusion of patients in the analysis. Whole body 18F-FDG-PET scans were performed 40 minutes following injection of 300-380 MBq of 18F-FDG. Images were reconstructed iteratively. In areas with focally elevated FDG uptake and in case of diffusely elevated intestinal 18F-FDG accumulation, standard uptake values (SUVs) were calculated. RESULTS: During a period of two years, five patients (one male, four female) with a mean age of 56.4 years (range 44-62) with a diagnosis of ETCL underwent 18F-FDG-PET. Four of these patients were imaged before application of cytotoxic treatment while one patient had regular PET scans for follow up. All four patients undergoing pre-therapeutic imaging showed markedly elevated intestinal 18F-FDG uptake, with a maximal SUV of 6.4-8.0 (mean 7.15 (SD 0.82)). The patient imaged following surgery and cytotoxic therapy had no pathologic 18F-FDG uptake which was found to correlate with normal duodenal mucosa, as evidenced by repeated biopsies and conventional imaging methods. During the same time span, 12 patients (five male, seven female) with a mean age of 63.8 years (range 42-82) suffering from CD were imaged. Four of these patients showed no elevated intestinal 18F-FDG uptake while five had minor diffuse intestinal 18F-FDG accumulation with SUVs ranging between 2.2 and 4.6 (mean 3.4 (SD 0.89)). In the remaining three patients with diffuse intestinal 18F-FDG uptake, no SUV could be calculated. SUVs in patients with ETCL were remarkably higher than in patients suffering from CD (p=0.011), irrespective of the activity of CD at the time of imaging. CONCLUSION: In spite of the relatively small number of patients, our results clearly indicate the potential value of 18F-FDG-PET for diagnosing and imaging ETCL. In addition, the data also suggest that 18F-FDG-PET may lead to early diagnosis in individuals developing ETCL in the context of longstanding CD. This is due to the fact that 18F-FDG does not appear to significantly accumulate in the gut of patients with CD, irrespective of disease activity.

Adult↗

Interface stress in polycrystalline materials: the case of nanocrystalline Pd.

Based on a generalization of a capillary equation for solids, we develop a method for measuring the absolute value of grain-boundary stress in polycrystalline samples having a large interface-to-volume ratio. The grain-boundary stress in nanocrystalline Pd is calculated from x-ray diffraction measurements of the average grain size and the residual-strain-free lattice spacings, yielding a value of 1.2+/-0.1 N/m. The random distribution of crystallite orientations in the sample suggests that this value is characteristic of high-angle grain boundaries in Pd.

Journal Article↗

[Development of macroglossia associated with neurosurgery in a seated position].

A case report is presented in which post-operatively a distinct macroglossia including an additional swelling running up to the trachea developed within the framework of a neurosurgical intervention in a seated position. Pathomechanisms and possible therapeutic methods are described and discussed with the help of a review of the literature.

Aged↗

[In vivo differentiation of pigmented skin tumors with laser Doppler perfusion imaging].

BACKGROUND AND OBJECTIVE: Malignant melanomas show a higher heterogeneity in their architecture and a higher vessel density because of neovascularization compared to benign melanocytic skin tumours. In this study the validity of the newly developed Laser Doppler Perfusion Imager (LDPI) with a lateral resolution of 100 microns in the differential diagnosis of pigmented skin tumours was investigated. PATIENTS/METHODS: The perfusion of 116 pigmented skin tumours was s measured with LDPI; 44 malignant melanomas, five melanoma metastases, 59 dysplastic nevi and eight basal cell carcinomas were studied before excision for precise histological diagnosis. RESULTS: There is a significantly higher perfusion of the malignant melanomas (3.15 +/- 1.87 AU) compared to dysplastic nevi (1.14 +/- 0.97 AU) (p < 0.01). By calculating a ratio of the mean perfusion in the tumour and the mean perfusion in adjacent healthy skin, the potential source of error because of regional differences in perfusion is eliminated. The ratio of malignant melanomas (10.78 +/- 9.18) is significantly higher than these of melanoma metastases (4.20 +/- 1.66), basal cell carcinomas (3.24 +/- 1.32) and dysplastic nevi (2.85 +/- 1.32). CONCLUSIONS: The high resolution LDPI has the potential to be a non-invasive screening method for preoperative differential diagnosis of pigmented skin tumours. Besides the epiluminescence microscopy and sonographic determination of the tumour thickness, we have now the possibility to get preoperative information about tumour vascularization.

Adult↗

[Collagenase 3 mRNA expression in squamous epithelial carcinomas of the oropharynx].

BACKGROUND: Metalloproteinases (MMP) are endopeptidases, which are able to degrade extracellular matrix. It is assumed that MMP play an important role in invasion and metastasis of malignomas. The expression of collagenase-3, also named MMP-13, was already detected in squamous cell carcinoma of the head and neck, but the significance in the process of metastasis is still unclear. PATIENTS AND METHODS: 36 tumor biopsies of oropharyngeal squamous cell carcinoma (10 cases N0, 26 patients N+) and 12 biopsies of normal oropharyngeal mucosa were analysed with reverse transcriptase-PCR and Northern Blot for their mRNA-expression of MMP-13 and TIMP-1, the physiological inhibitor of MMP-13. RESULTS: In 30 of 36 (83.3%) tumor biopsies a MMP-13-mRNA-expression was detected. In 9 of 10 (90%) cases with N0-status and 21 of 26 (80.7%) cases with N(+)-neck the mRNA-expression could be shown. There was no correlation between MMP-13-mRNA-expression and N-status. In 34 tumor biopsies (94.4%) a TIMP-1-expression was detected. MMP-13-mRNA was not detected in normal oropharyngeal mucosa. CONCLUSIONS: It seems that MMP-13-mRNA-expression is not a prognostic factor for metastatic behavior of oropharyngeal cancer and therefore not helpful for further decisions on the therapy.

Adult↗

[Difficulties in diagnosing an aortic arch thrombus].

INTRODUCTION: Thrombosis of the aortic arch is a rare and often underdiagnosed source of peripherical arterial embolic events. EXEGESIS: We report a case with a non-typical initial clinical presentation of polyarteritis nodosa. A mobile thrombus in the aortic arch was secondarily suspected when disseminated arterial embolism appeared. Transthoracic echocardiography failed twice to diagnosticate the source of embolism. The diagnosis was only performed with transesophageal echocardiography and confirmed by computed tomography and magnetic resonance imaging of the thoracic aorta. The thrombus completely disappeared after six months of oral anticoagulant therapy. CONCLUSION: Although rare, this diagnosis mustn't be disregarded in an etiologic view of recurrent and disseminated peripherical ischemic events (even clinically silent ones) under penalty of detrimental functional consequences due to a delayed diagnosis.

Aorta, Thoracic↗