Biomedical subjects

P Fritz

Publications and source records attributed to P Fritz.

At least 55 records · Page 3Linked to original sources

PubMed1998

Hemodynamic and hormonal changes during pneumoperitoneum and trendelenburg positioning for operative gynecologic laparoscopy surgery.

Objective: The number and types of surgical procedures being preformed using laparoscopic technique is increasing due to technological advances. Recent studies suggest the carbon dioxide pneumoperitoneum and patient positioning causes hemodynamic alterations, respiratory acidosis, and a release of stress hormones. However, to date, no studies have investigated the physiological effect of laparoscopic procedures lasting more than 60 minutes on the stress response and the effect of Trendelenburg positioning. The purpose of this study was to identify the physiological effect of pneumoperitoneum and positioning during prolonged laparoscopy on hemodynamic (cardiac index, mean arterial pressure, heart rate, systemic vascular resistance, and stroke volume), metabolic (arterial blood gases), and hormone (arginine vasopressin, aldosterone, and plasma renin activity) parameters. We hypothesized that pneumoperitoneum and patient positioning will alter the hemodynamic, hormone, and metabolic parameters.Methods: The study was longitudinal in design and sampled a total of 31 healthy subjects having a gynecologic oncologic laparoscopic procedure at Hurley Medical Center, Flint, Michigan. The subjects were randomly assigned one of three groups receiving an initial insufflation pressure of either 10, 15, or 18 mmHg. After obtaining informed consent hemodynamic, metabolic, and hormone measurements were obtained at the following times: 1) pre-induction, 2) post-induction, 3) post-insufflation, 4) post-Trendelenburg 5 minutes and at 30, 60, 90, and 120 minutes post-insufflation. The results were analyzed using multivariate analysis of variance for repeated measures with a P <.05. A power of 0.9 was obtained to identify changes over time.Results: During the time course of the study the hemodynamic, metabolic, and hormonal parameters showed significant alterations. The most dramatic hemodynamic changes occurred post-insufflation characterized by a decrease in cardiac index and stroke volume with a concurrent increase in systemic vascular resistance. The metabolic parameters showed a significant decrease in pH and corresponding increase in PaCO(2). However, the pH and PaCO(2) remained within normal limits through the study. As part of the study's protocol the investigators increased minute volume to control for a rise in PaCO(2) during the procedure. A significant increase was noted in aldosterone and arginine vasopressin at post-insufflation and Trendelenburg positioning. Plasma renin activity showed a dramatic increase following post-insufflation. None of the subjects developed any post anesthetic complications.Conclusion: Our study demonstrated that pneumoperitoneum and Trendelenburg positioning cause statistically significant elevations in the stress hormones and concurrently cause a decrease in hemodynamic parameters. A healthy patient may tolerate these changes but a patient with cardiovascular disease or pulmonary problems may not be able to compensate as efficiently.

Journal Article↗

PubMed1998

Simultaneous high-performance liquid chromatographic determination of a glucuronyl prodrug of doxorubicin, doxorubicin and its metabolites in human lung tissue.

A rapid and sensitive method was developed for the simultaneous determination of the new doxorubicin glucuronide prodrug HMR 1826, the parent drug doxorubicin and its metabolites in human lung tissue samples. Homogenization of frozen tissue samples with the micro-dismembrator was followed by a silver nitrate precipitation step. By removing the exceeding silver ions with sodium chloride further purification steps could be omitted. Compounds were separated by isocratic high-performance liquid chromatography on a LiChrospher 100 RP18 column and a mobile phase consisting of citric acid buffer-acetonitrile-methanol-tetrahydrofuran within 30 min and quantified with fluorescence detection. The method showed good recoveries for all compounds (86-99%) and a linear calibration range of 20 ng/g-80 microg/g for doxorubicin and 1-600 microg/g for HMR 1826.

Animals↗

PubMed1998

Expression of cyclooxygenase 1 and cyclooxygenase 2 in human synovial tissue: differential elevation of cyclooxygenase 2 in inflammatory joint diseases.

OBJECTIVE: To compare the expression of the cyclooxygenase (COX) isoforms, COX-1 and COX-2, in synovial tissue samples between patients with inflammatory arthritis (i.e., rheumatoid arthritis [RA], ankylosing spondylitis [AS], or psoriatic arthritis [PsA]) and patients with osteoarthritis (OA). METHODS: Paraffin-embedded sections of synovial tissue from patients with OA (n = 18), RA (n = 35), AS (n = 9), and PsA (n = 16) were immunostained for COX-1 and COX-2. Staining intensity was quantified videodensitometrically from specific synovial cell areas. In addition, samples of OA and RA synovial tissue were analyzed for levels of COX-1 and COX-2 messenger RNA (mRNA) using reverse transcriptase-polymerase chain reaction. RESULTS: Strong COX-2 immunostaining was observed in synovial blood vessel endothelium, synovial lining cells, chondrocytes, and subsynovial fibroblast-like cells in patients with inflammatory arthritides. In the blood vessels, the mean (+/-SD) optical density (MOD) of staining was elevated, especially in AS samples (2.73 +/- 0.63), but also in PsA (1.99 +/- 0.66) and RA samples (1.54 +/- 0.73), in comparison with OA synovial tissue (0.84 +/- 0.30; P < 0.01 versus other groups). COX-1 staining was almost exclusively localized in synovial lining cells, with no significant differences in the MOD between the diseases. COX-2 mRNA expression was higher in RA than in OA samples (P < 0.05). CONCLUSION: The expression of COX-2, but not the expression of COX-1, was found to be elevated in a disease-related pattern in the synovial tissue from patients with RA, AS, or PsA in comparison with OA samples, and was especially high in AS synovial tissue. These results may improve our understanding of the pathogenesis of different arthritic diseases, and may have implications for the use of selective COX-2 inhibitors in the treatment of inflammatory joint symptoms.

Adult↗

PubMed1998

[In vitro studies of PDR brachytherapy].

BACKGROUND: Calculations on the basis of the LQ-model have been focussed on the possible radiobiological equivalence between common continuous low dose rate irradiation (CLDR) and a superfractionated irradiation (PDR = pulsed dose rate) provided that the same total dose will be prescribed in the same overall time as with the low doserate. A clinically usable fractionation scheme for brachytherapy was recommended by Brenner and Hall and should replace the classical CLDR brachytherapy with line sources with an afterloading technique using a stepping source. The hypothes is that LDR equivalency can be achieved by superfractionation was tested by means of in vitro experiments on V79 cells in monolayer and spheroid cultures as well as on HeLa monolayers. MATERIALS AND METHODS: Simulating the clinical situation in PDR brachytherapy, fractionation experiments were carried out in the dose rate gradient of afterloading sources. Different dose levels were produced with the same number of fractions in the same overall incubation time. The fractionation schedules which were to be compared with a CLDR reference curve were: 40 x 0.47 Gy, 20 x 0.94 Gy, 10 x 1.88 Gy, 5 x 3.76 Gy, 2 x 9.4 Gy given in a period of 20 h and 1 x 18.8 Gy as a "single dose" exposition. As measured by flow cytometry, the influence of the dose rate in the pulse on cell survival and on cell cycle distribution under superfractionation was examined on V79 cells. RESULTS: V79 spheroids as a model for a slowly growing tumor, reacted according to the radiobiological calculations, as a CLDR equivalency was achieved with increasing fractionation. Rapidly growing V79 monolayer cells showed an inverse fractionation effect. A superfractionated irradiation with pulses of 0.94 Gy/h respectively 0.47 Gy/0.5 h was significantly more effective than the CLDR irradiation. This inverse fractionation effect in log-phase V79 cells could be attributed to the accumulation of cycling cells in the radiosensitive G2/M phase (G2 block) during protected exposure which was drastically more pronounced for the pulsed scheme. HeLa cells were rather insensitive to changes of fractionation. Superfractionation as well as hypofractionation yielded CLDR equivalent survival curves. CONCLUSIONS: The fractionation scheme, derived from the PDR theory to achieve CLDR equivalent effects, is valid for many cell lines, however not for all. Proliferation and dose rate dependend cell cycle effects modify predictions derived from the sublethal damage recovery model and can influence acute irradiation effects significantly. Dose rate sensitivity and rapid proliferation favour cell cycle effects and substantiate, applied to the clinical situation, the possibility of a higher effectiveness of the pulsed irradiation on rapidly growing tumors.

Animals↗

PubMed1998

Immunohistochemical localization of metallothionein in synovial tissue of patients with chronic inflammatory and degenerative joint disease.

Metallothioneins (MTs) are low-molecular-weight cytosolic proteins, which are thought to participate in metal homeostasis and protection against metal toxicity and oxidative stress. MT synthesis can be induced by a variety of inflammatory mediators and antirheumatic drugs, and high levels of MT have been implicated in resistance of cells to some antirheumatic drugs. We studied the expression and localization of MT in synovial tissue samples from patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or osteoarthritis (OA) by quantitative immunohistochemistry. Immunostaining for MT was detected in a large number of intimal lining cells in most of the investigated synovial tissue samples (75%). In a smaller proportion of samples (42%), some of the fibroblast-like cells of the subsynovial layer were also MT positive. Immunostaining and double-staining experiments with antibodies against monocyte-, macrophage- and leucocyte-associated antigens suggested that most of the MT-positive cells were intimal fibroblast-like cells and subsynovial fibroblasts. However, there were no statistically significant differences in the intensity of staining for MT between the rheumatic diseases and OA at the single-cell level. Thus, MT is expressed in synovial tissue and may participate in homeostatic and protective functions. The interindividual variability in the expression of MT in synovial tissue may be related to the therapeutic efficacy of the gold compounds and chemotherapeutic antirheumatic drugs sequestered by MT.

Adolescent↗

PubMed1998

Up-regulation of cytochrome P450 1A2, 2C9, and 2E1 in chronic pancreatitis.

The oxidative metabolism of xenobiotics is effected mainly by cytochrome P450 enzymes (CYP), which are expressed as a family of genetically related enzymes primarily in hepatocytes. The pancreas is among the extrahepatic tissues expressing CYP, and it has been suggested that intermediates generated by them might be of pathogenetic significance for diseases of the pancreas such as chronic pancreatitis. We studied 10 surgical resection specimens by immunohistochemistry with polyclonal antibodies against recombinant human CYP 1A1, 1A2, 2C9, 2E1, and 3A and used tissues from 11 normal pancreata as controls. In addition, we assayed microsomal preparations for their capacity to metabolize verapamil. In normal pancreata weak to moderate expression of all enzymes was demonstrated immunohistochemically in up to 50% of duct epithelia, acinar cells, and islet cells. In contrast, in chronic pancreatitis an up-regulation was observed, with immunohistochemical positivity in some cases in up to 100% of duct epithelia and acinar cells. The oxidative capacity of microsomal preparations from chronic pancreatitis was higher than that of preparations obtained from control tissues; compared to liver microsomes, however, it was low. The up-regulation of CYP may have pathogenetic significance for chronic pancreatitis. Yet considering the pancreas' capacity for conjugation reactions, conceivably low levels of reactive intermediates could effectively undergo inactivation.

Adult↗

PubMed1997

Enhanced uptake of doxorubicin into bronchial carcinoma: beta-glucuronidase mediates release of doxorubicin from a glucuronide prodrug (HMR 1826) at the tumor site.

Lack of tumor selectivity is a severe limitation of cancer chemotherapy. Consequently, reducing dose-limiting organ toxicities such as the cardiac toxicity of doxorubicin (Dox) is of major clinical relevance. Approaches that would facilitate a more tumor-selective anticancer therapy by using nontoxic prodrugs that are converted to active anticancer agents at the tumor site have been the subject of intensive research. One potential method to overcome the cardiac toxicity of Dox is to apply a nontoxic, glucuronide prodrug (HMR 1826) from which Dox is released by the action of beta-glucuronidase, an enzyme present at high levels in many tumors. Using a recently developed, isolated, perfused human lung model, we compared the uptake of Dox into normal lung and lung tumors after a 2.5-h lung perfusion with doxorubicin (n = 8) and with the novel doxorubicin glucuronide prodrug (n = 8). Dox showed a poor uptake into lung tumors as compared with normal lung [mean Dox concentration at the end of perfusion, 1.78 +/- 3.11 (median, 0.66) microg/g versus 22.03 +/- 10.4 (median, 18.5) microg/g; P < 0.001]. However, after perfusion with HMR 1826, the level of Dox in tumor tissue was about 7-fold higher than after perfusion with Dox itself [14.04 +/- 12.9 (median, 12.9) microg/g versus 1.78 +/- 3.11 (median, 0.66) microg/g, P < 0.05, n = 8]. In vitro experiments showed a significantly higher beta-glucuronidase expression and activity in the tumors. The extent of in vitro cleavage of HMR 1826 by homogenized lung tissue was closely related to the content of beta-glucuronidase (r = 0.9834, P < 0.0001). When D-saccharolactone, a specific inhibitor of beta-glucuronidase, was added to the perfusate containing HMR 1826, no accumulation of Dox in lung tissue was seen. These data indicate that the high Dox levels achieved in the tumors with HMR 1826 resulted from cleavage of the prodrug by beta-glucuronidase at the tumor site. Thus, the problem of poor Dox uptake into lung tumors could be circumvented by applying the doxorubicin glucuronide prodrug. Several lines of evidence based on both ex vivo and in vitro results indicate that the approach described using a glucuronide prodrug may be useful in facilitating more selective delivery of chemotherapy to tumors in humans.

Aged↗

PubMed1997

Consequences of optimization in PDR brachytherapy--is a routine geometrical optimization recommendable?

PURPOSE: On the basis of clinical examples for interstitial volume implants and surface molds the benefit and disadvantage of optimization in pulsed dose rate (PDR) brachytherapy using a stepping source was investigated. Geometrically optimized PDR dose distributions were compared with nonoptimized ones as produced by Ir wires. METHODS AND MATERIALS: In 25 patients who were treated with a double-plane interstitial breast implant with flexible catheters the first smoothly surrounding isodose, the reference volume and the uniformity and quality index derived from natural dose-volume histograms (Anderson) were considered. The effect of geometrical optimization on surface molds, which were used to irradiate chest wall relapses from breast cancer, was investigated by analyzing the reference surface, dose profiles, and depth-dose curves of a source arrangement covering an area of 10 x 10 cm2. RESULTS: Only in 3 of 25 patients the dose distribution of the volume implant was worsened by geometrical volume optimization regarding the homogeneity or the first smoothly surrounding isodose. Predominantly geometrical volume optimization reduced underdosage at the edges of the implants and improved the dose uniformity. The reference volume was increased. The geometrical distance optimization of surface mold dose distributions resulted in an enhancement of the reference surface and an improvement of the dose homogeneity on the skin surface. CONCLUSIONS: Geometrical optimization substantially changes the dose distribution. Only in a minority of cases the dose distributions of volume implants were worsened by geometrical volume optimization. Nevertheless, a close look at the results has to be recommended, especially if an overdosage in the lateral regions of the dose distribution and a dose falloff near the middle catheters is observed. The enhancement of the reference volume by geometrical volume optimization must be considered when choosing the active lengths. In surface mold treatment planning geometrical distance optimization is necessary to achieve homogeneous dose distributions for irradiation fields of different size and shape.

Brachytherapy↗

PubMed1997

Evaluation of synovial cytokine patterns in rheumatoid arthritis and osteoarthritis by quantitative reverse transcription polymerase chain reaction.

To compare the cytokine profile with the degree and composition of cellular infiltration in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium, synovial membranes from patients with RA (n = 14) and OA (n = 5) were examined, employing immunohistochemistry and competitive reverse-transcriptase polymerase chain reaction (RT-PCR), for interleukin (IL)-I beta, IL-2, IL-4, IL-5, IL-6, and IL-10, and tumour necrosis factor-alpha (TNF-alpha) gene expression. It was found that the strength of cytokine gene expression within the synovial membranes of patients with RA was not significantly correlated with the degree of synovial infiltration of T-cells, B-cells, or macrophages. No IL-2, IL-4, or IL-5 RNA was detected in the synovium of either RA or OA. Quantitative cytokine determination showed a similar pattern in RA and OA, although the two diseases differed in total synovial infiltration and the composition of infiltrating cellular elements. Thus the number of cell types known to produce certain cytokines does not appear to determine the strength of synovial cytokine expression measured by quantitative RT-PCR. Furthermore, the pattern of T-cell specific cytokines found in RA synovium does not accord with the concept of the TH0, TH1, and TH2.

Arthritis, Rheumatoid↗

PubMed1997

[Radiotherapy in the multimodal treatment of esophageal carcinoma. A review].

BACKGROUND: The curative potential of exclusively applied surgery or radiotherapy on esophageal carcinoma is exhausted. The 5-year survival rate of surgically treated esophageal carcinoma is stagnant at 20 to 30%, that for radiotherapeutically treated esophageal carcinoma at < or = 10%. The unchanged bad prognoses motivate the search for multimodal therapeutical concepts in order to improve the results of basic therapies. METHOD, RESULTS AND CONCLUSIONS: While neither perioperative radiotherapy nor perioperative chemotherapy were able to improve the treatment results significantly, a progress in the field of primary and preoperative radiochemotherapy emerges. On locally restricted tumors the latest findings show that a simultaneous radiochemotherapy with Cisplatin is more effective than radiotherapy alone. 20 to 30% histologically verified complete remissions can be reached through preoperative radiochemotherapy. These results will influence future treatment concepts. Brachytherapy can be taken into consideration in highly palliative situations as exclusive method of treatment or for support of laser treatment or bouginage for removal of stenosis. As the number of clinically controlled studies is not sufficient the importance of the brachytherapy boost for potentially curative intentions is not yet clear. Up to now the intraluminal hyperthermia is a underestimated method for improving the results of radiotherapy. Our overview summarizes all presently published randomized studies and relevant phase I/II-studies.

Antineoplastic Agents↗

PubMed1997

Combined endoluminal and external irradiation of inoperable oesophageal carcinoma.

PURPOSE: Higher radiation doses to oesophageal cancer might be possible by the steep dose gradient of an afterloading source. Structures at risk are not impaired by endoesophageal brachytherapy. Our experiences with endoesophageal afterloading in combination with external beam treatment are reported. METHODS AND MATERIALS: Fifty-four patients were treated by this technique. All patients suffered from an inoperable oesophageal carcinoma (7 adenocarcinoma, 47 squamous-cell carcinoma). Patients were scheduled by tumour stage and medical condition into a curative group (21 patients) and into a palliative group (33 patients). Mean sum doses of 60.3 Gy (range 58-70 Gy) percutaneously and an additional endoluminal dose of 13.6 Gy (range 10-20 Gy) were applied endoluminally in the curative group and 44.9 Gy (range 14-53 Gy) plus 17.5 Gy (range 5-30 Gy), respectively, in the palliative group. Overall treatment time was 10 weeks (range 4.6-14.3 weeks) for the curative group and 9.3 weeks (range 4.1-13.9 weeks) for the palliative group. RESULTS: Six weeks after the end of therapy a radiological remission could be observed in 32/33 of the palliatively treated patients (10 complete, 22 partial, 1 none). In 13 patients of this group a local progression was observed after a median time of 7.1 months. Median survival of this group was 9 months. A radiological remission occurred in 18/21 of the curatively treated patients (11 complete, 7 partial, 3 none). Median time to local progression (12 patients) was 4.5 months in this group and median survival was 7.7 months. The difference in time to progression reached a significant level (P = 0.05). The only favourable factors for survival were an incomplete or complete radiological remission (median survival 7.5 versus 11.4 months, P = 0.003) and stage I/II or III/IV (median survival 7.4 versus 12.6 months, P = 0.0024). The prior estimation of the treatment goal was not confirmed by survival data (curative, 7.7 months versus palliative, 9.0 months (not significant)). Eight of 54 minor and 8/54 (15%) major adverse events were observed. In four of these patients major complications were caused by progressive tumour. CONCLUSIONS: Endoesophageal afterloading combination with percutaneous irradiation is a feasible save treatment in inoperable cases. A good local tumour regression and functional results can be reached. The data suggest that higher endoluminal doses extend the time to local progression. In comparison with the literature survival can not be increased by this treatment technique. The best way to combine both treatment modalities has not yet been found.

Adult↗

PubMed1997

PDR brachytherapy with flexible implants for interstitial boost after breast-conserving surgery and external beam radiation therapy.

BACKGROUND AND PURPOSE: For radiobiological reasons the new concept of pulsed dose rate (PDR) brachytherapy seems to be suitable to replace traditional CLDR brachytherapy with line sources. PDR brachytherapy using a stepping source seems to be particularly suitable for the interstitial boost of breast carcinoma after breast-conserving surgery and external beam irradiation since in these cases the exact adjustment of the active lengths is essential in order to prevent unwanted skin dose and consequential unfavorable cosmetic results. The purpose of this study was to assess the feasibility and morbidity of a PDR boost with flexible breast implants. MATERIALS AND METHODS: Sixty-five high risk patients were treated with an interstitial PDR boost. The criteria for an interstitial boost were positive margin or close margin, extensive intraductal component (EIC), intralymphatic extension, lobular carcinoma, T2 tumors and high nuclear grade (GIII). Dose calculation and specification were performed following the rules of the Paris system. The dose per pulse was 1 Gy. The pulse pauses were kept constant at 1 h. A geometrically optimized dose distribution was used for all patients. The treatment schedule was 50 Gy external beam to the whole breast and 20 Gy boost. PDR irradiations were carried out with a nominal 37 GBq 192-Ir source. RESULTS: The median follow-up was 30 months (minimum 12 months, maximum 54 months). Sixty percent of the patients judged their cosmetic result as excellent, 27% judged it as good, 11% judged it as fair and 2% judged it as poor. Eighty-six percent of the patients had no radiogenous skin changes in the boost area. In 11% of patients minimal punctiform telangiectasia appeared at single puncture sites. In 3% (2/65) of patients planar telangiectasia appeared on the medial side of the implant. The rate of isolated local recurrence was 1.5%. In most cases geometrical volume optimization (GVO) yields improved dose distributions with respect to homogeneity and compensation of underdosage at the margins of the implant. Only in 9% of patients was the dose distribution impaired by GVO. However, GVO causes a number of substantial changes of the dose distribution which have consequences for its application. CONCLUSIONS: The interstitial CLDR boost of the breast can be replaced by the PDR technique without severe acute and late complications and without deterioration of the cosmetic results.

Adult↗

PubMed1997

Analysis of CYP2D6 expression in human lung: implications for the association between CYP2D6 activity and susceptibility to lung cancer.

We have studied whether CYP2D6 is expressed in human lung tissue, using a specific and sensitive reverse transcriptase-polymerase chain reaction method and immunohistochemistry. Seven out of the eight patients were extensive metabolizers as shown by genotyping for the CYP2D6 (debrisoquine-sparteine) polymorphism. To investigate whether expression of CYP2D6 in lung tumours is different from that in normal lung tissue, tumour tissue samples were also obtained from the same eight patients. Correctly spliced CYP2D6 mRNA was detected by RT-PCR analysis in human liver and duodenum but not in any of the lung samples. In accordance with these negative results, immunoreactivity for CYP2D6 protein, using specific monoclonal and polyclonal antibodies, was very low or absent. No specific cell type of lung tissue showed strong immunoreactivity for CYP2D6, although expression of CYP3A could be clearly demonstrated in the same tissue samples. Moreover, a Western blot analysis revealed no signal in lung microsomes from two additional extensive metabolizers. Taken together, these results indicate that expression of CYP2D6 in human lung is absent or very low. These findings thus argue against a significant local metabolic activation of procarcinogenic agents by CYP2D6 in the lung.

Aged↗

PubMed1997

-Apatite rheumatism, unusual aspects-.

Apatite calcifications may be responsible for unusual aspects. Clinically they may mimick sepsis or soft tissue tumor, and radiologically a bone tumor or soft tissue tumor-like lesion with respect to the erosion of the bone cortex adjacent to an unusual calcification. Diagnosis is based on knowledge of atypical sites of calcification, CT, and mainly, radiological regression of the calcification after a short follow-up.

Apatites↗

PubMed1996

First experiences with superfractionated skin irradiations using large afterloading molds.

PURPOSE: Radiotherapy of cutaneous metastases of breast cancer requires large radiation fields and high doses. This report examines the effectiveness and sequelae of superfractionated irradiation of cutaneous metastases of breast cancer with afterloading molds on preirradiated and nonirradiated skin. METHODS AND MATERIALS: A flexible reusable skin mold was developed for use with a pulsed (PDR) afterloader. An array of 18 parallel catheters was sewn between two foam rubber slabs 5 mm in thickness to provide a defined constant distance to the skin. By selection of appropriate dwell positions, arbitrarily shaped skin areas can be irradiated up to a maximal field size of 17 x 23.5 cm2. Irradiations are performed with a nominal 37 GBq 192Ir stepping source in pulses of 1 Gy/h at the skin surface. The dose distribution is geometrically optimized. The 80 and 50% dose levels lie 5 and 27 mm below the skin surface. Sixteen patients suffering from metastases at the thoracic wall were treated with 18 fields (78-798 cm2) and total doses of 40-50 Gy applying two PDR split courses with a pause of 4-6 weeks. Eleven of the fields had been previously irradiated with external beam therapy to doses of 50-60 Gy at 7-22 months in advance. RESULTS: For preirradiated fields (n = 10) the results were as follows: follow-up 4.5-28.5 months (median 17); local control (LC): 8 of 10; acute skin reactions: Grade 2 (moist desquamation) 2 of 10; intermediate/late skin reactions after minimum follow-up of 3 months: Grade 1 (atrophy/pigmentation): 2 of 10, Grade 2-3a (minimal/marked teleangiectasia): 7 of 10, Grade 4 (ulcer): 1 of 10; recurrencies: 2 of 10. For newly irradiated fields (n = 7) results were: follow-up: 2-20 months (median 5); LC: 6 of 7; acute reactions: Grade 1: 4 of 7, Grade 2: 3 of 7; intermediate/late skin reactions after minimum follow-up of 3 months (n = 5): Grade 2-3a: 2 of 5; recurrencies: 0 of 7. Local control could be achieved in 82% of the mold fields. Geometric optimization was mandatory to achieve a homogeneous dose distribution on the skin. CONCLUSION: Superfractionated brachytherapy with skin molds is an effective alternative for the treatment of skin metastases of breast cancer even if the skin is preirradiated. This method is economically advantageous compared to external beam therapy, which would require several weeks. At the curved chest wall, optimized molds can provide better dose homogeneity than abutted electron fields. Skin reactions are comparable to the sequelae of orthovolt irradiation. In preirradiated areas, PDR doses should be restricted to 40-45 Gy. PDR doses of 50 Gy seem to be the limit for tolerance even in previously unirradiated fields.

Adult↗

PubMed1996

Expression of cytochrome P 450 3A enzymes in human lung: a combined RT-PCR and immunohistochemical analysis of normal tissue and lung tumours.

We have previously demonstrated expression of cytochrome P 450 3A (CYP3A) protein in pulmonary carcinomas and surrounding normal tissue, using immunohistochemistry. These results suggested that different CYP3A enzymes may be expressed in normal and tumour tissue. Therefore, the aim of the present study was to identify specific CYP3A enzymes expressed in normal human lung and lung tumours. Both normal lung tissue and tumour tissue from eight patients was analyzed for CYP3A4, CYP3A5 and CYP3A7 mRNA using a specific RT-PCR (reverse transcriptase-polymerase chain reaction) method. Identical samples were subjected to immunohistochemical analysis of CYP3A protein. CYP3A5 was the major enzyme of the CYP3A subfamily present at the mRNA level in both normal human lung and lung tumours. CYP3A5 mRNA was detected in normal lung tissue in all eight cases and in tumour tissue in four cases. CYP3A7 mRNA was detected in five cases in normal tissue and in one tumour. Notably, no CYP3A4 mRNA was found in any of the samples. Immunohistochemical staining for CYP3A protein was found in normal lung tissue in each case. Interestingly, all pulmonary carcinomas showed immunostaining for CYP3A, while mRNA for CYP3A enzymes was found in only four cases. In summary, our study indicates a specific expression pattern of the members of the CYP3A subfamily in normal human lung and lung tumours. These findings have potential clinical significance, since it has been recently shown that CYP3A5 catalyzes the activation of the anticancer pro-drugs cyclophosphamide and ifosfamide. Thus, local activation of these agents may take place in pulmonary carcinomas and surrounding normal tissues.

Aged↗

PubMed1996

Quantitative photometrical assessment of iron deposits in synovial membranes in different joint diseases.

We investigated 86 synovial membranes from patients suffering either from rheumatoid arthritis (RA) or osteoarthritis (OA). Iron deposits in the synovial membrane were stained by the Prussian blue reaction, and the amount of stained iron was quantitatively assessed by microscope photometry. We found a statistically significant increase in iron deposits in the synovial membrane of RA patients when compared to OA patients. The amount of iron deposits correlated with the histological subtype of synovitis, those presenting with more exudative and proliferative features showing greater amounts of iron deposits. We also observed an inverse correlation between the haemoglobin concentration and erythrocytes in the serum and the amount of iron in the synovial membrane. From our data we concluded that iron deposits in the synovial membrane can contribute by several mechanisms, including activation of oxygen radicals, to the chronic inflammatory reaction in RA synovitis.

Aged↗

PubMed1996

Immunohistochemical detection of factor XIIIa and factor XIIIs in synovial membranes of patients with rheumatoid arthritis or osteoarthritis.

In spite of differences in etiology, RA and OA lead to astonishingly similar synovitic alterations. Fibroblastic transformation of the synovial membrane and an increase in monocytes constitute a rare but highly characteristic feature of RA. Monocytes synthesize factor (F) XIII, implying that FXIII (a and s) in synovial tissue might help to differentiate between RA and OA. Biopsies were obtained at open surgery from 98 unselected patients with the clinical diagnosis of RA (n = 54) or OA (n = 44). In a three-stage (ABC) immunoperoxidase technique, polyclonal antisera against factor XIIIa and factor XIIIs were investigated. Compared to OA sections. RA synovium showed more FXIIIa-positive cells-monocytes, fibrocytes, fibroblasts and synovial lining cells. In the subsynovial layer, band-like structure of FXIIIa-stained cells was observed in 27.8% of the RA patients, but in only one OA specimen. Higher proportions of FXIIIa-positive monocytes, macrophages, histiocytes and fibroblasts, as well as positive Langhans giant cells and vascular wall regions (except endothelial cells), were observed in RA. OA specimens revealed more intense FXIIIa labeling of these cells with a lower percentage of stained cells. Overall, labeling with FXIIIs antibody resulted in less intense staining. In conclusion, distinction between synovitis caused by RA and synovitis due to OA is possible, as the former show higher numbers of FXIIIa-positive cells, including monocytes, fibroblasts, fibrocytes and synovial lining cells. Further more, RA tissue is stained less intensely than OA tissue. There is evidence for continuous excretion of FXIII in the synovial membrane by the above-mentioned cell systems.

Adolescent↗