Biomedical subjects
Publications and source records attributed to D Schuster.
The anatomy of the lateral cervical region is described and revisited. The three topographical regions where the neurovascular bundle can be easily compressed by surrounding structures are highlighted. Furthermore, the paper focuses on the anatomical variations which are able to produce a thoracic outlet syndrome (TOS).
OBJECTIVE: To evaluate the long-term effects of antiretroviral treatment (ART) interruptions on metabolic, immunological, virological and clinical outcomes in chronically HIV-1 infected patients. METHODS: Multi-centric, prospective, controlled 24-month cohort study in HIV-1 infected patients interrupting ART once or several times and for at least two weeks. Patients were compared to a frequency-matched control group continuing on ART. RESULTS: A total of 399 HIV-1 infected patients were included, among them 133 patients with treatment interruption (TI) and 266 control patients. Baseline characteristics were well matched. Median baseline CD4 cell count was 379/microl in TI-patients and 410/microl in control patients (p = ns). Median duration of the first TI was 1.1 months, and 37 % of patients had two or further TI's. Whereas CD4 cell count in control patients had increased significantly by a median of 67/microl at month 24 (p<0.0001), median CD4 cell count at month 24 in the TI-patients did not differ significantly from baseline. However, two-year AIDS-free survival was not significantly different between TI- and control patients. Liver enzymes and blood lipids improved significantly during TI. CONCLUSION: TI was associated with a significant immunological disadvantage at 24-month follow-up compared to continued ART. In this relatively immunocompetent cohort, however, TI's did not lead to an increased risk of disease progression within two years of follow-up.
Efavirenz and nevirapine are frequently used drugs in antiretroviral therapy. Rashes are common side effects of these drugs. In this study, we examined the characteristics of efavirenz- and nevirapine-associated rashes. This prospective nonrandomized multicenter study included 662 HIV-infected patients (efavirenz: 325, nevirapine: 337) to determine incidence, duration, cross-reactivity, and outcome upon reexposure. Of the treated patients, 4.5% (n=30) developed rashes (nevirapine: 2.4% and efavirenz: 6.4%). In four patients treatment was not interrupted. Three patients were re-exposed to the initial drug without any side effects. Therapy with nevirapine or efavirenz does not have to be interrupted if rashes exhibit no blistering, mucosal manifestations, or systemic signs.
Over 90% of the market withdrawals were caused by drug toxicity. Hepatotoxicity and cardiovascular toxicity proved to be the major causes for two out of three market withdrawals in the respective time period. In clinical phases I-III 43% of drug development project terminations were due to insufficient efficacy of the investigated compound. The second important issue, which caused one third of the projects to be closed, was toxicity. ADME parameters and economic and other reasons played a minor role. The results of our study indicate that compared with previous studies on this subject, no major improvements have been achieved in the last decade.
Practical applications of structured illumination microscopy (SIM) often suffer from various artefacts that result from imprecise instrumental hardware and certain bleaching properties of the sample. These artefacts can be observed as residual stripe patterns originating from the illumination grating. We investigated some significant causes of these artefacts and developed a correction approach that can be applied to images after acquisition. Most of the artefacts can be attributed to changes in illumination and detection intensities during acquisition. The proposed correction algorithm has been shown to be functional on noisy image data, and produces exceptional, artefact-free results in everyday laboratory work.
PURPOSE: To show Didanosin in a new formulation as a once-a-day capsula as a well-tolerated and effective HIV-therapy when used in a protease sparing regimen including genotypic resistance pattern in blood, semen and cerebrospinal fluid before and during treatment. METHOD: Two groups of 58 patients, each containing 9 patients who had not been previously treated with any antiretroviral medication, and 49 patients heavily pretreated for 3,7 (DDI group) and 2,8 (non-DDI group) years, have been followed up for at least half a year. A group of 24 patients taking a special combination of Didanosin plus Efavirenz and Stavudine have been analysed with genotypic resistance testing concerning viral load response and resistance pattern under therapy. RESULTS: Suppression of plasma HIV-1 RNA to <50 copies/mL and <500 copies/mL in the DDI group was achieved in 74% and 84% of the pretreated patients, respectively, and in 100% of the naive patients after 24 weeks. In the non-DDI group suppression was achieved in 59% and 69% of the pretreated patients, respectively, and in also 100% of the naive patients. The viral load reduction in the DDI containing regimen at week 24 was 1.7 log subset 10 for the pretreated and 3,4 log subset 10 for the naive patients. In the non-DDI group, the reduction was 1.5 for the pretreated and 4,0 for the naive patients. CD4 cell counts increased from 440 to 517 cells/microL at week 24 for the pretreated, and from 171 to 289 for the naive patients in the DDI containing regimen. In the other group, cells increased from 396 to 406 for the pretreated and from 155 to 321 for the naive patients. In each group, 12 patients discontinued treatment; 4 patients in the DDI group and 7 patients in the non-DDI group because of adverse events. There were no AIDS-defining events in the antiretroviral-treated patients in both groups. 16 patients of the special combination group (DDI, D4T and EFV) were evaluated for more than 24 weeks. Suppression of HIV-1 RNA to <50 copies /mL were found in 75% of the naive and 43% of the pretreated patients. No relevant mutations were found during treatment. CONCLUSION: The new formulation of Didanosin as a once-a-day capsula in a protease sparing regimen was well-tolerated, effective in reducing viral load and in preventing AIDS-defining events. The combination of DDI, D4T and EFV proved to be a potent therapy without developing relevant mutations.
African Americans (AA) have greater prevalence of type 2 diabetes mellitus (DM), and nondiabetic AA have demonstrated increased insulin resistance when compared with Caucasian Americans (CA). The objective of this study was to examine the impact of chronic use of an insulin sensitizer on glucose metabolism in normal glucose tolerant AA at risk for DM (previous gestational diabetes mellitus [GDM] or first-degree relative with DM). Forty-nine high-risk AA received 200 mg/d troglitazone (TRO) versus 81 age-, weight-, and body mass index (BMI)-matched high-risk AA who received placebo (PLA) for 24 months. Yearly anthropometric measurements, oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIVGTT) were performed. Biochemical parameters were monitored quarterly. There was no significant change in anthropometric measurements over 24 months in TRO versus PLA. There were no significant differences in serum glucose, insulin, or C-peptide incremental area under the curve (AUC) in TRO versus PLA at baseline or 24 months for OGTT and FSIVGTT. The insulin sensitivity (S(I)) for TRO and PLA increased from baseline to 24 months by 17% and 16%, respectively. The TRO demonstrated a 26% increase in insulin/glucose ratio versus 1% increase in the PLA at 24 months. The disposition index (DI) increased 33% from baseline in TRO versus 21% increase in PLA. Modest improvement in glucose metabolism was seen in TRO when compared with PLA. TRO was well tolerated without significant reported adverse events. Based on our current data, the treatment of normal glucose tolerant high-risk AA with thiazolidinedione (TZD) may be beneficial to "reset" and protect glucose metabolism by improving insulin responses. Because of the potential drug-related risks associated with use of TZD and the proven positive impact of diet and exercise in prevention of DM, studies of longer duration with examination of other potentially beneficial parameters, such as cardiovascular indices and inflammatory markers will be necessary to justify the cost in the nondiabetic population.
Acute urinary retention in children may be associated with a broad spectrum of different causes. Acute appendicitis or acute ovarian torsion are rare and complicate the diagnosis. The case of a 6-year-old girl with urinary retention caused by ovarian torsion is reported, in which clinical presentation showed nonspecific complaints and ultrasound demonstrated a retrovesical mass. The long-standing ovarian torsion could only be diagnosed by laparotomy. This case once again demonstrates possible difficulties in obtaining a correct diagnosis, especially when imaging techniques reach their limits. Here, the anatomical structures had become so altered by adhesions of the omentum that they were no longer identifiable, rendering the advantageous, non-invasive laparoscopy ineffective. As a result, laparotomy became the most accurate and reliable method for obtaining a correct diagnosis. The occurrence of acute urinary retention with ovarian torsion can be explained by an earlier disturbance of the vegetative nervous system.
For deconvolution applications in three-dimensional microscopy we derived and implemented a generic, accelerated maximum likelihood image restoration algorithm. A conjugate gradient iteration scheme was used considering either Gaussian or Poisson noise models. Poisson models are better suited to low intensity fluorescent image data; typically, they show smaller restoration errors and smoother results. For the regularization, we modified the standard Tikhonov method. However, the generic design of the algorithm allows for more regularization approaches. The Hessian matrix of the restoration functional was used to determine the step size. We compared restoration error and convergence behaviour between the classical line-search and the Hessian matrix method. Under typical working conditions, the restoration error did not increase over that of the line-search and the speed of convergence did not significantly decrease allowing for a twofold increase in processing speed. To determine the regularization parameter, we modified the generalized cross-validation method. Tests that were done on both simulated and experimental fluorescence wide-field data show reliable results.
To determine the therapeutic effect of sulfur amino acid supplementation in HIV infection we randomized 40 patients with antiretroviral therapy (ART; study 1) and 29 patients without ART (study 2) to treatment for 7 months with N-acetyl-cysteine or placebo at an individually adjusted dose according to a defined scheme. The main outcome measures were the change in immunological parameters including natural killer (NK) cell and T cell functions and the viral load. Both studies showed consistently that N-acetyl-cysteine causes a marked increase in immunological functions and plasma albumin concentrations. The effect of N-acetyl-cysteine on the viral load, in contrast, was not consistent and may warrant further studies. Our findings suggest that the impairment of immunological functions in HIV+ patients results at least partly from cysteine deficiency. Because immune reconstitution is a widely accepted aim of HIV treatment, N-acetyl-cysteine treatment may be recommended for patients with and without ART. Our previous report on the massive loss of sulfur in HIV-infected subjects and the present demonstration of the immunoreconstituting effect of cysteine supplementation indicate that the HIV-induced cysteine depletion is a novel mechanism by which a virus destroys the immune defense of the host and escapes immune elimination.
Pneumoparotid is considered to be a rare entity, but the diagnosis might not be as uncommon as reported. We report a case in which computed tomography incidentally revealed air in the parotid ducts bilaterally. Treatment is aimed at the elimination of predisposing and causative factors, but because our patient denied any symptoms or precipitating factors and had a benign presentation, no immediate intervention was initiated.
Whenever using modern stereological methods for estimating number-weighted or volume-weighted mean volumes of biological particles such as cell nuclei, either 'isotropic uniform random' (IUR) tissue sections or 'vertical' ones had to be used. However, with the currently available procedures and tools it was virtually impossible to prepare such sections from small specimens such as the mouse brain. Here, a modification of the 'isector' is presented, which allows the embedding of mouse brain halves into paraffin spheres as a useful basis for preparing IUR sections. By using this modified isector it could be shown for various types of neurons in the hippocampus and cerebellum of young adult mice, that there are no differences between estimated mean nuclear volumes obtained on IUR sections and those obtained on conventional frontal or sagittal ones. This result may be used to expand the interpretation of estimated mean nuclear volumes of the types of neurons investigated here.
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The effectiveness of cabbage leaf extract was compared with that of a placebo in treating breast engorgement in lactating women. In a double-blind experiment with a pretest/posttest design, 21 participants received a cream containing cabbage leaf extract, while 18 received placebo cream. The placebo group received equal relief to the treated group, with the two groups showing no difference on all outcome measures. However, mothers perceived both creams to be effective in relieving discomfort. Feeding had a greater effect than the application of cream on relieving discomfort and decreasing tissue hardness. It is therefore recommended that lactation consultants encourage mothers to breastfeed if possible to relieve the discomfort of breast engorgement.
The present study investigated the ability of uteroferrin and recombinant bovine granulocyte monocyte/macrophage-colony stimulating factor (rbGM-CSF) to modulate the myelosuppressive effects of 5-fluorouracil (5-FU) in young female pigs (Sus scrofa). Pigs (N = 3/treatment) were infused with 5-FU (32.5 mg/kg) on days 0 and 1 of the experimental period. Uteroferrin (100 micrograms/kg in 0.9% NaCl), rbGM-CSF (10 micrograms/kg in 0.9% NaCl), uteroferrin + rbGM-CSF (as above) or control (0.9% NaCl) were administered as intramuscular injections twice daily (0800 and 2000 hr). Peripheral blood cell number, composition, and progenitor cells were determined over 28 days. Treatment of pigs with 5-FU resulted in a rapid leukocytopenia and thrombocytopenia (nadirs on days 5 and 7, respectively) and a modest decrease (P < 0.05) in red blood cell (RBC) number (nadir on day 14). Although nor affecting RBC and thrombocytes, treatment of pigs with uteroferrin had an initial protective effect (P < 0.05) on the 5-FU-induced leukocytopenia (63 and 64 vs 48 and 39 +/- 6% of baseline on days 3 and 5, respectively). In contrast, rbGM-CSF enhanced (P < 0.05) the rate of the leukocytopenia and had only minor effects on thrombocyte numbers relative to controls. These effects appeared to be additive, as pigs treated with uteroferrin + rbGM-CSF had a reduced rate of leukocytopenia compared to pigs treated with rbGM-CSF alone. Uteroferrin + rbGM-CSF also attenuated (P < 0.05) the suppression and enhanced (P < 0.05) recovery of RBC and thrombocyte numbers following 5-FU treatment. In control pigs, a modest rebound leukocytosis (122 +/- 6% of baseline) and thrombocytosis (141 +/- 9% of baseline) was evident. Uteroferrin enhanced (P < 0.05) the rebound leukocytosis (135 +/- 6% of baseline), but attenuated (P < 0.05) the thrombocytosis. In contrast, rbGM-CSF enhanced (P < 0.05) the duration of the leukocytosis during the recovery phase, an effect augmented by the combination of uteroferrin + rbGM-CSF. In addition, treatment with uteroferrin + rbGM-CSF resulted in a sustained thrombocytosis (days 12 to 21). As indicated by changes in CFU-GM, BFU-E, and CFU-GEMM progenitor cells in peripheral blood, the effects of uteroferrin and rbGM-CSF appeared to reflect their ability to enhance the proliferation and/or differentiation of both similar and distinct hematopoietic progenitor cells.
The present study investigated the effect of uteroferrin and recombinant bovine granulocyte-monocyte/macrophage colony stimulating factor (rbGM-CSF) on hematopoiesis in young female pigs. Uteroferrin (100 micrograms/kg in 0.9% NaCl), rbGM-CSF (10 micrograms/kg in 0.9% NaCl), uteroferrin + rbGM-CSF (as above), or control (0.9% NaCl) were administered as intramuscular injections twice daily (0800 and 2000 hr). Peripheral blood cell number, composition, and progenitor cells were determined over 28 days. Uteroferrin had minimal effects on white blood cell (WBC) number, while rbGM-CSF caused both a rapid (days 2-7; maximum 122 +/- 8% of baseline) and late (days 16-28; maximum 133 +/- 8% of baseline) increase in WBC. Combination treatment with uteroferrin + rbGM-CSF abolished the initial increase in WBC number,but resulted in a prolonged increase in WBC number (days 14-28) relative to control. The rbGM-CSF-induced increase in WBC number resulted from rapid increases (P < 0.05) in monocytes and neutrophils. The addition of uteroferrin + rbGM-CSF enhanced (P < 0.05) the initial increase in the monocyte population and augmented the neutrophilia. In addition, uteroferrin + rbGM-CSF resulted in a dramatic eosinophilia (days 2-28), which was not detected in either the uteroferrin or rbGM-CSF treatments. Although not substantially affected by uteroferrin alone, rbGM-CSF caused an increase (P < 0.05) in thrombocyte numbers from days 1 through 9 (maximum 133 +/- 11% of baseline), an effect augmented by cotreatment with uteroferrin. The ability of these cytokines to modulate blood cell number and composition appeared to result from their effects on hematopoietic progenitor cells. Treatment of pigs with uteroferrin increased (P < 0.05) CFU-GEMM, CFU-GM, and BFU-E progenitor cells in peripheral blood, while rbGM-CSF caused increases (P < 0.05) relative to control in CFU-GM and CFU-GEMM. These effects were additive, as uteroferrin + GM-CSF augmented the increases in CFU-GM, BFU-E, and CFU-GEMM. Collectively, these results indicate that uteroferrin and rbGM-CSF can modulate hematopoiesis in young pigs. These effects were both additive and, in the case of neutrophils and eosinophils, synergistic. Hence, the mechanism(s) by which uteroferrin and rbGM-CSF modulate hematopoiesis appear to be different.
In this paper a brief description of a computer and robotic aided surgery system is given with a detailed overview of the necessity to develop special tools for robotic surgery. The application range of this robotic system has been specially focused on the orthopaedics field and, more particularly, on the execution of osteotomies. It was therefore necessary to develop a new saw device which would meet medical and--from the robot system point of view--mechanical as well as functional requirements. After describing the device which was developed on the basis of these requirements, a detailed comparative study of off-the-shelf oscillating saws and the new device is given at the end of the paper.
This study compared the effectiveness of chilled and room temperature green cabbage leaves in reducing the discomfort of breast engorgement in postpartum mothers. Twenty-eight lactating women with breast engorgement used chilled cabbage leaves on one breast and room-temperature cabbage leaves on the other for a two-hour period. Pre-treatment pain levels were compared with post-treatment levels for both conditions. There was no difference in the post-treatment ratings for the two treatments; mothers reported significantly less pain with both treatments. We concluded that it is not necessary to chill cabbage leaves before use.