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Biomedical subjects

P Schmid

Publications and source records attributed to P Schmid.

At least 37 records · Page 2Linked to original sources
PubMed2002

High-dose chemotherapy in high-risk primary breast cancer.

The role of high-dose chemotherapy (HDCT) in high-risk primary breast cancer remains controversial. Although results of 8 randomized trials on HDCT in high-risk early-stage breast cancer have become available, the data are still inconclusive. Only one trial revealed a significant benefit in recurrence-free survival for patients treated with HDCT and neither of the 8 trials showed a significant improvement in overall survival. However, interpretation of the data is limited due to a lack of statistical power in some of the trials, a relatively short follow-up, a relatively intensive chemotherapy regimen in the control arm and an inappropriate selection of cytotoxic agents with only moderate activity and/or unacceptable toxicity. The results of ongoing studies are therefore urgently needed to determine the role of HDCT in the management of primary breast cancer. With respect to the substantial morbidity and treatment-related mortality, HDCT should not be considered standard for the treatment of breast cancer outside clinical trials, unless a clear advantage in overall can be demonstrated compared to conventional chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Prediction of response to hormonal treatment in metastatic breast cancer.

Prediction of outcome and individualization of therapeutic strategies are challenging problems in oncology. Predictive parameters for response to hormonal treatment include the expression of hormone receptor, the extent and location of metastatic spread, disease-free interval, patient age, response to prior hormonal therapy, grading, and more recently, some molecular markers like the expression of HER-2/neu. The use of conventional statistics for prediction of response to hormonal treatment is limited by non-linearities and complex interactions between predictive factors. Modern computational mathematical models like artificial neural networks, entropy-based inductive algorithms or chi(2) interaction detection algorithms can describe these interactions and generate classification models and decision structures. They can be used to predict the clinical outcome for individual patients. In contrast to conventional methods, the level of confidence for the predictions can reach 90% and more. This might be an important step towards further individualization of therapeutic strategies.

Antineoplastic Agents, Hormonal↗
PubMed2002

Proteoglycan deposition around chondrocytes in agarose culture: construction of a physical and biological interface for mechanotransduction in cartilage.

With a view towards the development of methods for cartilage tissue engineering, matrix deposition around individual chondrocytes was studied during de novo matrix synthesis in agarose suspension culture. At a range of times in culture from 2 days to 1 month (long enough for cartilage-like material properties to begin to emerge), pericellular distributions of proteoglycan and matrix protein deposition were measured by quantitative autoradiography, while matrix accumulation and cell volumes were estimated by stereological methods. Consistent with previous work, tissue-average rates of matrix synthesis generally decreased asymptotically with time in culture, as de novo matrix accumulated. Cell-scale analysis revealed that this evolution was accompanied by a transition from predominantly pericellular matrix (within a few microm from the cell membrane) deposition early in culture towards proteoglycan and protein deposition patterns more similar to those observed in cartilage explants at later times. This finding may suggest a differential recruitment of different proteoglycan metabolic pools as matrix assembly progresses. Cell volumes increased with time in culture, suggestive of alterations in volume regulatory processes associated with changes in the microphysical environment. Results emphasize a pattern of de novo matrix construction which proceeds outward from the pericellular matrix in a progressive fashion. These findings provide cell-scale insight into the mechanisms of assembly of matrix proteins and proteoglycans in de novo matrix, and may aid in the development of tissue engineering methods for cartilage repair.

Animals↗
PubMed2001

Relationship between salivary progesterone, 17-hydroxyprogesterone, and cortisol levels throughout the normal menstrual cycle of healthy postmenarcheal girls.

OBJECTIVE: To determine the usefulness of salivary P and 17 alpha-hydroxyprogesterone (17-OHP) for the assessment of ovarian function. In addition, salivary cortisol (F) levels were measured to assess the role of the adrenal cortex throughout the menstrual cycle. DESIGN: Prospective study. SETTING: Outpatients in hospital for children and adolescents. PATIENT(S): Thirty young women with regular menstrual cycles. INTERVENTION(S): Saliva collection in the early morning from day 1 of menstrual bleeding until next menses. MAIN OUTCOME MEASURE(S): Salivary P, 17-OHP, and F measured by RIAs. RESULT(S): During days 1-12 of the follicular phase, P and 17-OHP levels remained unchanged (P: 9-29.3 pg/mL; 17-OHP: 8-31 pg/mL). Thereafter, P increased exponentially from day 13 onward, reaching a plateau (mean +/- SEM, 70.1 +/- 9.0 pg/mL) between day 16 and 20, followed by a constant decrease until end of the cycle. The 17-OHP levels increased between day 14 and 17 (maximum: 45.8 +/- 4.5 pg/mL), decreasing rapidly thereafter. The F levels remained unchanged (follicular: 7.5 +/- 1.1 ng/mL; luteal 7.2 +/- 1.1 ng/mL). There was a significant correlation between P and 17-OHP (r(2) = 0.43; P<.001). When calculating ratios of P/F and 17-OHP/F, linear regression yielded a much stronger correlation (r(2) = 0.74; P<.001), although F did not show any correlation to P or 17-OHP. CONCLUSION(S): Changes in salivary 17-OHP levels throughout the menstrual cycle reflect ovarian but not adrenal function.

17-alpha-Hydroxyprogesterone↗
PubMed2001

mGlu5 receptors and nociceptive function II. mGlu5 receptors functionally expressed on peripheral sensory neurones mediate inflammatory hyperalgesia.

Previous studies have demonstrated that the metabotropic glutamate receptor subtype 5 (mGlu5 receptor) is expressed in the cell bodies of rat primary afferent neurones. We have further investigated the function and expression of mGlu5 receptors in primary afferent neurones, and their role in inflammatory nociception. Freund's complete adjuvant-induced inflammatory hyperalgesia of the rat hind paw was significantly reduced by intraplantar, but not by intracerebroventricular or intrathecal microinjection of the selective mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP). Pharmacological comparison in vivo of the nociceptive effects of glutamate, and ionotropic and metabotropic glutamate (mGlu) receptor agonists applied to the rat hind paw, indicated that group I mGlu receptor agonists induce a dose-dependent decrease in paw withdrawal threshold (mechanical hyperalgesia). Group I mGlu agonist-induced hyperalgesia was inhibited by co-microinjection of MPEP, but not by the mGlu1 receptor antagonist (S)-4-carboxy-phenylglycine (4-CPG). Carrageenan-induced inflammatory hyperalgesia was inhibited by pre-treatment of the inflamed hind paw with MPEP, but not following MPEP injection into the contralateral hind paw. Dorsal horn neurones receiving peripheral nociceptive and non-nociceptive afferent input were recorded in anaesthetized rats following microinjection of CHPG into their peripheral receptive fields. CHPG significantly increased the frequency and duration of firing of dorsal horn wide dynamic range (WDR) neurones and this activity was prevented by co-administration of CHPG and MPEP into their receptive fields. Immunohistochemical experiments revealed the co-expression of mGlu5 receptor protein and betaIII tubulin in skin from naive rats, indicating the constitutive expression of mGlu5 receptors on peripheral neurones. Double-labelling of adult rat DRG cells with mGlu5 receptor and vanilloid receptor subtype 1 antisera also supports the expression of mGlu5 receptors on peripheral nociceptive afferents. These results suggest that mGlu5 receptors expressed on the peripheral terminals of sensory neurones are involved in nociceptive processes and contribute to the hyperalgesia associated with inflammation.

Analgesics, Opioid↗
PubMed2001

Achievement of complete remission in refractory Hodgkin's disease with prolonged infusion of gemcitabine.

Although, in recent decades effective chemotherapy regimens have been developed for the treatment of Hodgkin's disease, the prognosis of patients who experience disease progression is still very poor. New treatment approaches are urgently required to salvage such patients. In a patient with Hodgkin's disease who failed to achieve complete remission with the escalated BEACOPP protocol, progression with bone marrow infiltration and B symptoms developed despite further treatment. Subsequently, gemcitabine was administered in a novel schedule as a four-hour infusion of 250 mg/m2 on days 1, 8, and 15, every four weeks. After the first cycle, the dose was reduced to 200 mg/m2 because of grade 3 neutropenia. The condition of the patient improved after the second cycle and no toxicity was observed during cycles 3-6. Complete remission was achieved. Two years after the end of gemcitabine therapy, the patient is in good clinical condition and in continuous complete remission without further treatment. This is the first report of the prolonged infusion of gemcitabine as a salvage therapy in Hodgkin's disease.

Adult↗
PubMed2000

[New therapeutic approaches in advanced breast carcinoma. Palliative measures are increasingly more tolerable].

Advances in palliative chemotherapy are based on the development of new substances or new treatment strategies, such as, for example, high-dose chemotherapy. New cytostatic agents are developed with the aim of improving therapeutic efficacy and tolerability. Taxanes rapidly became part of standard treatment, and their combination with the anthracyclines represents the most effective treatment currently available. Liposomal encapsulation of anthracyclines can reduce their cardiotoxicity without loss of efficacy. Recent antimetabolites and the vinca alkaloid, vinorelbine, combine a good antitumoral effect with a favorable toxicity profile. The use of the monoclonal antibody, trastuzumab, has made specific immunotherapy possible for the first time. The role of high-dose chemotherapy remains uncertain, and further randomized studies are urgently needed.

Administration, Oral↗
PubMed2000

[Unaltered homocysteine levels during simvastatin therapy].

Homocysteinemia is regarded as a risk factor for vascular disease. Several risk factors and diseases, but also various drugs, amongst them some lipid lowering medications, have been shown to increase plasma homocysteine concentrations. We therefore assessed the influence of simvastatin on plasma homocysteine levels in 57 patients suffering from severe familial heterozygous hypercholesterolemia. After 1, 3 and 6 months of simvastatin therapy plasma homocysteine levels did not show any change compared to the levels before therapy. Males had typically higher homocysteine levels than females and concentrations in smokers were in most subgroups significantly higher than in non-smokers. No difference in patients taking either 20 or 40 mg simvastatin was apparent and no correlation to the lipid lowering action was found. These findings indicate that in contrast to a number of other lipid lowering agents, simvastatin does not affect plasma homocysteine levels.

Adult↗
PubMed2000

Antibiotic prophylaxis for appendectomy in children: critical appraisal.

Prophylactic antibiotics are widely used during surgery, above all for clean-contaminated or contaminated procedures. Because factors other than the degree of contamination play a critical role in regard to postoperative infectious complications, it is not evident that recommendations for antibiotic prophylaxis for an adult population can be transferred to children. The aim of the study was to analyze the incidence of postoperative infections in children undergoing appendectomy for suspected appendicitis to evaluate critically the effectiveness of prophylaxis. The charts of all children undergoing appendectomy between 1988 and 1998 were analyzed. In general, appendectomies were performed without antimicrobial prophylaxis. If a perforated appendicitis was found at operation, antibiotics were given intraoperatively. Postoperative infectious complications were defined as wound infections, intraabdominal infections, or prolonged postoperative pyrexia. During the study period of 10 years, 954 patients underwent appendectomy. In 24% of cases the appendix was perforated. Patients received prophylactic antibiotics at the surgeon's discretion. These patients were excluded from further analysis. Among those with non-perforated appendicitis (n = 633), Infectious complications occurred in 19 (3%). Analyzing subgroups according to histologic diagnosis, the incidence was 4.2% (16/382) for gangrenous appendicitis and 1.2% (3/251) for simple appendicitis or normal appendix. These figures are clearly lower than those reported from an adult population, indicating that results from adults cannot a priori be transferred to children, and that general recommendations concerning antimicrobial prophylaxis must be considered carefully for this age group.

Antibiotic Prophylaxis↗
PubMed2000

New therapeutic approaches in primary systemic AL amyloidosis.

Primary systemic AL (amyloid light-chain) amyloidosis is a plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure. The prognosis of primary amyloidosis is generally poor, with a median survival of 1-2 years. There is no available treatment which improves impaired organ function by induction of amyloid mobilization. Since amyloidosis is a dynamic process, measures that reduce the supply of the amyloid fibril precursor protein can result in a major regression of the deposits. Conventional-dose melphalan can prolong the median duration of survival from 8.5 to 18 months, but the clinical response rates with improvement of impaired organ function are low and the response is slow. Preliminary data suggest that VAD is effective in AL amyloidosis. Up-front high-dose chemotherapy with autologous peripheral blood stem cell transplantation can result in an improvement of the patient's clinical condition, but the treatment-related toxicity can be high, owing to impaired organ function. The use of VAD followed by high-dose chemotherapy is the concept of a German trial. The improvement of the patient's condition prior to high-dose chemotherapy by induction of a remission with VAD might reduce the transplantation-related morbidity and mortality in amyloidosis.

Amyloid↗
PubMed2000

Further evidence for oxidant-induced vascular endothelial growth factor up-regulation in the bronchoalveolar lavage fluid of lung cancer patients undergoing radio-chemotherapy.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of physiological and neoplastic blood vessel growth. Moreover, in vitro studies have demonstrated that VEGF can be up-regulated by conditions associated with the generation of free radicals and reactive oxygen species. In a previous study we reported on strongly increased VEGF concentrations in the bronchoalveolar lavage fluid (BALF) of patients with lung cancer under therapy. In this study we aimed to reveal whether this increase was due to the therapy-associated intrapulmonary oxidative burden. PATIENTS AND METHODS: A total of 103 BALF samples from 94 patients with lung cancer (82 patients with non-small-cell lung cancer, 12 patients with small-cell lung cancer) were studied at different times before, during or after cancer treatment. VEGF levels in the lavage fluid and ratios of oxidised methionine in proteins of epithelial lining fluid (ELF) were determined. RESULTS: As reported previously, strongly increased VEGF levels in the ELF were observed in patients undergoing chemotherapy when radiotherapy had been administered before. Increased levels of oxidised methionine indicated that these patients suffered from severe pulmonary oxidative stress that was significantly less in patients undergoing only chemotherapy. Similarly, VEGF concentrations in the ELF were significantly elevated in cancer patients at the time of diagnosis, but the oxidised methionine levels did not reveal significant oxidant/antioxidant imbalances in these patients. CONCLUSION: Systemic chemotherapy is associated with oxidative stress in vivo, which is more pronounced if patients are additionally treated with radiation. VEGF levels in the ELF are increased by this condition as well as by the activity of the tumour itself.

Adult↗
PubMed2000

Longitudinal threshold changes in older men with audiometric notches.

Age-related hearing loss (presbycusis) is a multifactorial process that results chiefly from the accumulating effects of noise damage and aging on the cochlea. Noise damage is typically evidenced clinically by a discrete elevation (notch) of the auditory thresholds in the 3-6 kHz region of the audiogram whereas aging affects the highest frequencies first. To determine whether the presence of such high-frequency notches influences auditory aging, we examined the 15 year change in audiometric thresholds in 203 men from the Framingham Heart Study cohort. The mean age at the first hearing test was 64 years (range 58-80). Occupational and recreational noise exposure over the 15 years was assumed to be minimal due to the age of the subjects. The presence or absence of a notch was determined using a piecewise linear/parabolic curve fitting strategy. A discrete elevation of the pure-tone thresholds of 15-34 dB in the 3-6 kHz region was deemed a small notch (N1), and elevations of 35 dB or greater were deemed large notches (N2). Absence of a notch (N0) was encoded those ears with <15 dB elevation in the 3-6 kHz region. The presence and absence of notches correlated with the subjects' history of noise exposure. The 15 year pattern of change in age-adjusted pure-tone thresholds varied significantly by notch category. There was less change over time in the notch frequencies (3-6 kHz) and significantly greater change in the adjacent frequency of 2 kHz in the N2 group as compared to the N0 and N1 groups. The adjacent frequency of 8 kHz showed a significant, but smaller, change in the N1 group as compared to the N0 and N2 groups. The change at 2 kHz was independent of the starting hearing level at E15, whereas the changes at 4-8 kHz were influenced by the hearing level at E15. These data suggest that the noise-damaged ear does not 'age' at the same rate as the non-noise damaged ear. The finding of increased loss at 2 kHz suggests that the effects of noise damage may continue long after the noise exposure has stopped. The mechanism for this finding is unknown but presumably results from prior noise-induced damage to the cochlea.

Aged↗
PubMed2000

Detection of HMGI-C in the peripheral blood of breast cancer patients.

The human high mobility group (HMG) protein (HMGI-C) belongs to the HMG family of architectural transcription factors which are expressed only during embryonic development, and not in normal adult tissues. Considerable interest has recently been shown in HMGI-C and its expression in a variety of neoplastic tissues, whereas no expression could be found in normal tissue adjacent to the tumour. So far, no data is available on the expression of HMGI-C in the peripheral blood of patients with solid tumours. In this study we analysed the expression of HMGI-C in peripheral blood samples of 61 patients with breast cancer and 35 healthy donors using a haemi-nested reverse transcriptase-polymerase chain reaction (RT-PCR) technique. No HMGI-C could be detected in any of the healthy donors' samples. In the three prognostic groups according to the Nottingham Prognostic Score, the proportion of patients expressing HMGI-C differed significantly (P=0.001). The worse the prognosis was, the more patients expressed HMGI-C. This is the first report on the expression of HMGI-C in the peripheral blood of patients with breast cancer and our data suggest that this expression is correlated with a poor prognosis.

Adult↗
PubMed2000

Modelling of soft tissue deformation for laparoscopic surgery simulation.

Virtual reality based surgical simulator systems offer a very elegant solution to the development of endoscopic surgical trainers. While the graphical performance of commercial systems already makes PC-based simulators viable, the real-time simulation of soft tissue deformation is still the major obstacle in developing simulators for soft-tissue surgery. The goal of the present work is to develop a framework for the full-scale, real-time, finite element simulation of elastic tissue deformation in complex systems such as the human abdomen. The key for such a development is the proper formulation of the model, the development of scalable parallel solution algorithms, and special-purpose parallel hardware. The developed techniques will be used for the implementation of a gynecological laparoscopic VR-trainer system.

Computer Simulation↗