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Biomedical subjects

M Frick

Publications and source records attributed to M Frick.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of intravenous magnesium on heart rate and heart rate variability in patients with chronic atrial fibrillation.

The present double-blind, placebo-controlled study investigated the effects of intravenous magnesium on heart rate and rate variability in 30 patients with chronic atrial fibrillation. During standardized conditions, intraindividual variation in heart rate and rate variability was low in patients with chronic atrial fibrillation and magnesium had no effect on heart rate or rate variability.

Aged↗
PubMed1999

Factors influencing G-CSF-mediated mobilization of hematopoietic progenitor cells during steady-state hematopoiesis in patients with malignant lymphoma and multiple myeloma.

We retrospectively analyzed factors influencing PBPC mobilization during steady-state hematopoiesis in 52 patients with malignant lymphoma (n=35) or multiple myeloma (n=17) who received 77 cycles of G-CSF (12.5-50 microg G-CSF/kg/day). For 15 of these patients, the first mobilization cycle (12.5 microg G-CSF/kg/day) was followed by a second course with an increased dose of G-CSF (25 or 50 microg/kg/day). Leukapheresis was started on day 4, about 2 h after s.c. G-CSF administration, and repeated on 2-5 consecutive days. CD34+ cells were determined by flow cytometry in each apheresis product and in the peripheral blood prior to G-CSF administration, beginning on day 4. Colony assays were performed on cryopreserved samples prior to autografting. In the 15 patients receiving two mobilization cycles the higher G-CSF dose was associated with higher levels of CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful (>2x10(6) CD34+ cells/kg) collections (p=0.058). Patients with limited previous cytotoxic therapy (n=19, up to six cycles of a standard regimen such as CHOP and/or less than 20% marrow irradiation) who received a daily dose of 12.5 microg G-CSF/kg had higher levels of circulating CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful collections (p<0.05) compared with patients previously treated with more intensive radiochemotherapy (n=15). Ten of 20 patients (50%) who failed during the first cycle were successful during subsequent cycles with escalated doses of G-CSF. Trough levels of circulating CD34+ cells on day 4 were predictive for success or failure to achieve >2x10(6) CD34+ cells/kg, especially in heavily pretreated patients. In conclusion, a daily dose of 12.5 microg G-CSF/kg seems sufficient to mobilize PBPC during steady-state hematopoiesis in the majority of patients who have received limited previous radiochemotherapy. Higher doses of G-CSF, up to 50 microg/kg/day, mobilize more PBPC and should be considered for patients previously treated with intensive radiochemotherapy or those failing to mobilize sufficient numbers of CD34+ cells with lower doses of G-CSF.

Adult↗
PubMed1999

Early low-dose dobutamine echocardiography predicts late functional recovery after thrombolyzed acute myocardial infarction.

BACKGROUND: This study was undertaken to evaluate the ability of predischarge low-dose dobutamine echocardiography to predict late left ventricular functional recovery after thrombolyzed acute myocardial infarction. METHODS AND RESULTS: Low-dose dobutamine echocardiography was performed in 54 patients 4 +/- 2 days after acute myocardial infarction treated with thrombolysis. Follow-up resting echocardiography was carried out in 49 of these patients at a mean of 18 +/- 6 months later. Viability was defined as recovery of myocardial function at follow-up, expressed as an improvement of wall motion of at least 1 grade or more in at least 2 contiguous infarct zone segments. In 24 of the 49 patients (group I), wall motion at follow-up improved in comparison with the early resting echocardiographic study (1.72 +/- 0.29 vs 1.37 +/- 0.34, P <.001). In the remaining 25 patients (group II), no wall motion enhancement was seen at follow-up (1.57 +/- 0.38 vs 1.58 +/- 0.36, NS). In 22 of the 24 patients in group I, early low-dose dobutamine echocardiography showed improvement in the wall motion score index compared with baseline resting measurements (1.72 +/- 0.29 vs 1.44 +/- 0.24, P <.001). The positive and negative predictive value of early low-dose dobutamine echocardiography to predict functional recovery was 76% and 92%, respectively. CONCLUSION: Predischarge low-dose dobutamine echocardiography is an accurate tool for detecting viable myocardium and predicting late left ventricular recovery after acute myocardial infarction treated with thrombolysis.

Adrenergic beta-Agonists↗
PubMed1999

Threshold calcium levels for lamellar body exocytosis in type II pneumocytes.

Pulmonary surfactant is secreted via exocytosis of lamellar bodies (LBs) by alveolar type II cells. Here we analyzed the dependence of LB exocytosis on intracellular Ca(2+) concentration ([Ca(2+)](i)). In fura 2-loaded cells, [Ca(2+)](i) was selectively elevated by flash photolysis of a cell-permeant caged Ca(2+) compound (o-nitrophenyl EGTA-AM) or by gradually enhancing cellular Ca(2+) influx. Simultaneously, surfactant secretion by single cells was analyzed with the fluorescent dye FM 1-43, enabling detection of exocytotic events with a high temporal resolution (T. Haller, J. Ortmayr, F. Friedrich, H. Volkl, and P. Dietl. Proc. Natl. Acad. Sci. USA 95: 1579-1584, 1998). Exocytosis was initiated at a threshold concentration near 320 nmol/l with both instantaneous or gradual [Ca(2+)](i) elevations. The exocytotic response to flash photolysis was highest during the first minute after the rise in [Ca(2+)](i) and thus almost identical to purinoceptor stimulation by ATP. Correspondingly, the effects of ATP on initial secretion could be sufficiently explained by its ability to mobilize Ca(2+). This was further demonstrated by the fact that exocytosis is significantly blocked by suppression of the ATP-induced Ca(2+) signal below approximately 300 nmol/l. Our results suggest a highly Ca(2+)-sensitive step in LB exocytosis.

Adenosine Triphosphate↗
PubMed1998

Long-term induction of a unique C1- current by endothelin-1 in an epithelial cell line from rat lung: evidence for regulation of cytoplasmic calcium.

1. Using conventional microelectrodes, the perforated patch clamp technique and fluorescence microscopy with fura-2, we investigated the relationship between the cell membrane potential, whole-cell currents and the free cytoplasmic Ca2+ concentration ([Ca2+]i) in response to 10 nM endothelin-1 (ET) in a rat respiratory epithelial cell line (L2). 2. Microelectrode experiments revealed that ET caused an immediate depolarization of the cell membrane potential (Vm) by 25 mV, which was unaffected by Na+ replacement with N-methyl-D-glucamine+ (NMDG+) or by omission of bath Ca2+. In contrast, ET depolarized the cells by 61 mV in the presence of low C1- (6 mM), resulting in a complete breakdown of Vm. 3. In perforated patch clamp experiments, the ET-induced whole-cell current (IET) exhibited a slight outward rectification with a reversal potential (Vrev) of -22.7 mV. IET was reduced by 85 % in low C1- (6 mM), but was unaffected by Ca2+ removal, Na+ replacement with NMDG+, pipette K+ replacement with Cs+ or 1 mM Ni2+ in the bath. 4. IET was unaffected by (+)-isradipine (100 nM), a specific L-type Ca2+ channel (L-VDCC) blocker. Transient inward Sr2+ currents through L-VDCCs were blocked by ET. 5. ET induced a biphasic Ca2+ signal, consisting of a 'peak' and a 'plateau' elevation of [Ca2+]i. Simultaneous patch clamp and fura-2 measurements revealed that IET coincided with intracellular Ca2+ release but clearly outlasted the elevation of [Ca2+]i. When the rise of [Ca2+]i was prevented by pretreatment with thapsigargin in a Ca2+-free bath, both activation time and amplitude of IET were reduced. Under these conditions, ET caused a decrease of [Ca2+]i. 6. The C1- channel blocker mefenamic acid (MFA) had a dual, concentration-dependent effect on both IET and the ET-induced 'plateau' elevation of [Ca2+]i: an increase at 10 microM, but an almost complete block at 100 microM. The effect of MFA on IET preceded the effect on [Ca2+]i. 7. The ET-induced 'plateau' [Ca2+]i fell below control values in a low-C1- (6 mM) solution. 8. These data indicate an amplifying function of intracellular Ca2+ release on an otherwise Ca2+-independent, unique C1- current by ET. Moreover, this C1- current appears to be functionally coupled with dihydropyridine (DHP)-insensitive Ca2+ entry, suggesting a modulatory role for long-lasting effects of ET.

Animals↗
PubMed1998

[Studies with high-dose chemotherapy and subsequent autologous stem cell transplantation in breast carcinoma].

Survival rates for several subgroups of patients with breast cancer treated with conventional therapy remain poor. Only about 30% of patients with primary breast cancer involving more than 9 axillary lymph nodes remain disease-free at 5 years from diagnosis despite surgery, conventional-dose chemotherapy and radiotherapy. Metastatic breast cancer with 5 year survival rates of about 3% generally represents incurable disease. Chemotherapeutic agents are conventionally limited by side effects. The easy procurement of haematopoietic stem cell support through mobilization of peripheral blood progenitors has spurred the development of new strategies employing high-dose treatment for treatment of high risk breast cancer. Autologous stem cell support antagonizes chemotherapy-induced myelotoxicity and thereby allows dose escalation by a factor of 1.5 to about 20. Pilot studies evaluating significant dose escalation in adjuvant treatment of patients with advanced disease have resulted in an apparent improvement in event-free survival rates to over 70%. Repetitive applications of chemotherapy at myeloablative doses are now increasingly being used. Data from prospectively randomized phase III trials will not be available before the end of 1998. For metastatic breast cancer one prospective, randomized clinical trial has been published. Results are significantly better for patients who have been treated by high-dose chemotherapy compared to patients who received conventional polychemotherapy (median survival 90 vs. 45 weeks). For methodological reasons (small patient numbers, patient selection, weak standard therapy etc.) results from the trials cited above are under discussion. Until publication of further results from ongoing phase III trials HDC for breast cancer remains experimental and should not be given outside of clinical trials.

Antineoplastic Agents↗
PubMed1997

[Significance of stem cell-supported high-dose chemotherapy in the treatment of gynecological malignancies: indications and current clinical trials in the Federal Republic of Germany].

The use of hematopoetic growth factors and stem cell support reduces the dose limiting hematopoetic toxicity's, resulting in a remarkable increase in dose intensity of chemotherapy. As far as data from phase I/II trials are available high dose chemotherapy (HDC) may be integrated in the systemic treatment of breast and ovarian cancers. In metastatic breast cancer HDC may induce fairly high but short response rates. Long term survival is expected in 20% of the cases. Patients with limited metastatic disease, without significant prior chemotherapy, partial or complete response to induction chemotherapy and complete remission after HDC may benefit from HDC. In phase I/II trials HDC improved recurrence free survival in high risk patients (e.g. > 9 positive LN) compared to historic controls and may therefore be a curative approach. Ovarian cancer is very chemosensitive. Conventional chemotherapies induce multidrug resistance rapidly. Just as in breast cancer-Phase I/II trials demonstrated high response rates to HDC, which again were short of duration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Idarubicin, melphalan and cyclophosphamide: an intensified high-dose regimen for the treatment of myeloma patients.

Following conventional chemotherapy, eight myeloma patients presenting with advanced tumor stages were treated with an intensified high-dose regimen and autologous peripheral blood stem cell transplantation. High-dose chemotherapy consisted of idarubicin 20 mg/m2 on days -13, -12 and -11, melphalan 100 mg/m2 on days -5 and -4 and cyclophosphamide 60 mg/kg (plus mesna 60 mg/kg) on days -3 and -2 (IMC). Seven patients achieved a complete remission or a very good partial remission (reduction of M-component > or =90%). There were no toxic deaths. Severe mucositis and fever of unknown origin were seen in all patients. Reversible supraventricular tachycardias without clinical signs of cardiac failure occurred in five patients. One patient developed a persistent deterioration of cardiac function. We surmise that high-dose chemotherapy with IMC is very effective and well tolerated in myeloma patients.

Adult↗
PubMed1991

Identification and characterization of proteinase K-resistant proteins in members of the class Mollicutes.

Proteins resistant to proteinase K are rare because of the potency, wide pH optimum, and low peptide bond specificity of this enzyme. Previously, only the prion proteins associated with transmissible spongiform encephalopathies, possibly related proteins in the mollicute Spiroplasma mirum, and proteinase K itself have been reported. We identified a new proteinase K-resistant protein, p40-pr, in two strains of Mycoplasma hyorhinis and in extracts of these organisms. p40-pr's are similar to prion proteins in their resistance to high doses of proteinase K and in the reversal of this resistance by strong denaturing conditions. However, p40-pr's were distinct immunologically, in relative molecular mass, and in their method of extraction. Two immunologically related forms of p40-pr were identified on sodium dodecyl sulfate (SDS) gels and Western immunoblots, a 40-kDa species in boiled samples and a 120-kDa species dissociable by boiling in SDS. Reduction with 2-mercaptoethanol did not affect the mass of p40-pr's or the 120-kDa forms. The development of proteinase K resistance of p40-pr correlated to age-dependent increases in organism protein-lipid ratios. p40-pr-like proteinase K-resistant proteins of 46 to 50 kDa were identified in four of eight additional species of the class Mollicutes but not in S. mirum. However, these mycoplasmal proteins did not react with antibody to the denatured 40-kDa form of M. hyorhinis p40-pr purified by electroelution. The chromatographically purified 46-kDa proteinase K-resistant protein of Mycoplasma orale was an arginine deiminase.

Animals↗
PubMed1990

Involvement of older drivers in multivehicle side-impact crashes.

Side impacts were studied using three separate analyses. National Accident Sampling System (NASS) and National Crash Severity Study (NCSS) cases were reviewed on multivehicle crashes involving fatal chest and abdominal injury by interior contact. Twenty-five cases were analyzed and showed an unusually high involvement of older occupants. Analyses of the 1975-1986 FARS confirmed an overinvolvement. Sixty-four percent of near-side seated occupants were over 50 years old and 36% over 70 in fatal multivehicle side impacts. In contrast, 26% of victims in single-vehicle frontal crashes were over 50 and 8% over 70 years old. Analysis of the 1982-1986 NASS showed that single-vehicle side impacts are not an important injury risk for older drivers, except on icy or wet roads. In contrast, the risk of injury in multivehicle side impacts increases steadily with age and is a major problem for older drivers. The individual NASS and NCSS cases also showed that 88% of the multivehicle side crashes took place at an intersection and that the driver of the struck vehicle frequently caused the crash by driving error (48%) or traffic violation (16%). The majority of cases occurred in daylight hours, on dry roads, and without alcohol involvement. Changes in visual perception, judgment and attention of the older driver may be factors in their missing a traffic signal or turning in front of traffic under the right-of-way. In addition, a reduced tolerance to impact force probably contributes to the injury. Although an analysis of photographs of the side-impacted vehicle indicated that 44% had side-structure deformation that was similar to that produced in the National Highway Traffic Safety Administration (NHTSA) moving deformable barrier test, only 24%-32% of the cases actually addressed the proposed NHTSA dynamic side-impact test. The results of this analysis bear on the agency's preliminary regulatory impact analysis.

Abdominal Injuries↗
PubMed1987

Separation of multiple components of HeLa cell nuclear extracts required for pre-messenger RNA splicing.

Components essential for nuclear pre-messenger RNA splicing have been partially purified from HeLa cell nuclear extracts by chromatography on DEAE-Sepharose, heparin-Sepharose, Mono Q, and Mono S. We have obtained six fractions which, when combined, efficiently splice a synthetic adenovirus 2 major late RNA substrate in vitro. All fractions contain components that support the formation of splicing intermediates (the cleaved 5' exon and the intron-exon 2 lariat). At least one of the fractions also contains an activity that is essential for the second step in the splicing reaction, namely cleavage at the 3' splice site and exon ligation. Two of the fractions are enriched in the major small nuclear ribonucleoprotein particles U1, U2, U4/U6, and U5. They participate in the formation of the splicing complexes which precedes the cleavage and ligation reactions. The remaining four fractions appear to contain protein factors, as suggested by their resistance to micrococcal nuclease.

Chromatography, Gel↗
PubMed1987

Local antibodies to alpha-casein and beta-lactoglobulin in the saliva of infants.

Salivary antibodies were studied in 112 infants between 1 day and 8 yr of life. SIgA anticasein was present from birth in breast-fed and bottle-fed infants. Bottle-feeding resulted in significantly higher concentrations of SIgA anticasein at 3 wk to 3 months of life as compared to breast-feeding. Salivary anticasein declined toward the end of the 1st yr and was present in less than half of the children older than 1 yr. Salivary anti-beta-lactoglobulin was also present at birth in some infants. Levels increased slightly over the following 3 months but remained low. Only a minority of older children had this antibody in their saliva.

Animals↗
PubMed1984

Opiate induced feeding is not dependent on the hippocampus.

It has been shown that spreading depression of the hippocampus can elicit feeding, and that several opioid peptides elicit spreading depression when injected into the hippocampus. To determine whether such depression is the primary mechanism by which opiates induce feeding, we tested the feeding effects of naloxone, an opiate antagonist, and butorphanol tartrate, a kappa-sigma agonist, on feeding in rats with and without hippocampal lesions. Naloxone tended to reduce intake approximately equally in the two groups. Similarly, the doses of butorphanol that increased intake in sham rats were equally effective in lesioned rats. It was concluded that the hippocampus is not the major structure mediating opiate-induced feeding.

Animals↗