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Biomedical subjects

P Fritz

Publications and source records attributed to P Fritz.

At least 91 records · Page 5Linked to original sources

Differential expression of drug metabolizing enzymes in primary and secondary liver neoplasm: immunohistochemical characterization of cytochrome P4503A and glutathione-S-transferase.

The question whether expression of drug metabolizing enzymes in human liver is altered by liver neoplasm remains controversial; however, the ability or unability of tumour cells to metabolize certain drugs may be important for developing therapeutic strategies. We therefore investigated the abundance and localization of two classes of drug metabolizing enzymes [cytochrome P4503A (CYP3A) and pi-type glutathione-S-transferase] by means of immunohistochemistry (standard ABC technique) in patients with hepatocellular carcinoma (HCC, n = 16) and with liver metastasis from adenocarcinoma (n = 53) in comparison to normal controls (n = 5). The distribution of CYP3A in normal liver samples showed a characteristic pattern of four to five layers of stained hepatocytes surrounding the central vein. Eleven out of 16 cases of HCC showed expression of CYP3A; staining was less intense than in normal liver and zonation was completely lost. In contrast, only 5 out of 53 samples of metastasis stained positively for CYP3A. The difference between primary and secondary neoplasm was statistically significant (chi-square, P < 0.0001). Pi-type glutathione-S-transferase (GST) stained positively in 9 out of 16 HCC and in 48 out of 53 cases of liver metastasis (chi-square, P < 0.01) indicating a higher percentage of immunostaining in liver metastasis. In summary, we observed differences in the abundance and distribution pattern of CYP3A and GST between primary and secondary neoplasma of human liver and in comparison to normal controls. In combination with established methods these data may contribute to the establishment of reliable test systems for distinguishing primary from secondary liver tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Increased dose-rate effect in V79-multicellular aggregates (spheroids). Relation to initial DNA lesions and repair.

Survival of exponentially growing V79 monolayer cells was measured after irradiation at low dose-rate (up to 1.1 Gy/h) and at high dose-rate (2.5 Gy/min) and compared to corresponding survival data of V79 spheroid cells. The so-called contact effect, the increased radioresistance of cells irradiated in spheroids, was expressed to a greater extent with low dose-rate exposure. Lesion fixation by hypertonic treatment was more pronounced in spheroid versus monolayer cells and abolished the contact effect. The reduced radiosensitivity of V79 spheroid cells could not be related to a reduced number of initial DNA lesions or a higher capacity to rejoin DNA breaks (measured by neutral elution). These findings suggest that the ratio of lesion repair to fixation/misrepair may differ between cells from spheroids and monolayer culture thus influencing the response of cells to dose-rate changes differentially.

Animals↗

Epidermal Langerhans cells in uremic patients on hemodialysis or continuous ambulatory peritoneal dialysis.

Skin biopsies of 33 uremic patients-13 patients on continuous ambulatory peritoneal dialysis (CAPD), 12 on hemodialysis (HD), 8 patients with end-stage renal disease (ESRD) before initiation of dialysis treatment-and 10 healthy volunteers were investigated to determine the number of Langerhans cells (LC) by light microscopy after staining for S-100 protein. The epidermal LC count was significantly lower in patients on CAPD (mean: 62.9 LC/mm2; p = 0.027) and patients on HD (mean: 30.4 LC/mm2; p = 0.0015) compared to controls (mean: 110.1 LC/mm2) and uremic patients before initiation of dialysis treatment (mean: 122.6 LC/mm2). The difference between LC counts of CAPD and HD patients did not reach statistical significance (p = 0.057). There was no relation between LC count and age (p = 0.057) or epidermal width (p = 0.26). No statistically significant correlation could be demonstrated between duration of dialysis and LC count (r = -0.33, p = 0.10). LC counts of CAPD patients with diabetes mellitus (n = 7) were not significantly different from those of nondiabetics (n = 6; p = 0.77). LC counts seem to be normal in uremic patients before dialysis treatment. The reduction in LC density in the skin of dialysis patients may contribute to immunodeficiency of uremic patients on regular dialysis treatment.

Adult↗

Developmental risk factors in postpartum women with urine tests positive for cocaine.

The aim of the study was to ascertain whether there was a difference in developmental experiences between two groups of inner city postpartum patients, those who used cocaine during pregnancy and those who did not. A retrospective structured interview was administered to 80 postpartum women examining demographic characteristics, adaptive function, drug use patterns, and selected risk factors for adult substance abuse encountered before age 16. The sample was divided into two cohorts of women: 40 women identified by urine tests of their babies as using cocaine shortly before delivery and a comparison group of 40 women not identified by positive urines. Comparisons between the two cohorts revealed that the cocaine identified women had significantly higher overall past and present use of a broad range of drugs, particularly crack and other forms of cocaine, as well as lower levels of general adaptive functioning despite the fact that they were demographically comparable. When compared to the nonusers, they displayed markedly elevated scores on measures of developmental risk factors for adult substance use. This study highlights the importance of early developmental risk factors on later drug use during pregnancy and general adult adaptive functioning. Further study and intervention targeted at persons with these risk factors are warranted.

Adult↗

Nucleolar organizer regions in human breast cancer.

The silver staining technique for demonstration of argyrophilic nucleolar organizer regions (AgNORs) was examined for their usefulness in routine clinical diagnosis for discrimination of benign breast diseases from malignant ones and for prognostic purposes. We examined the number of AgNORs in 56 cases of malignant breast lesion and 20 cases of benign breast disease, using routinely fixed material. We found a clear-cut difference between benign breast diseases as compared with breast carcinomas where the mean AgNOR count was significantly higher, whereas no statistically significant correlation was observed between AgNOR counts and survival rate of human breast cancer patients.

Adenocarcinoma, Mucinous↗

[Rheumatological complications of dialysis].

The articular complications observed in dialysed chronic renal failure failures, whose incidence increases with the duration of dialysis, are closely correlated with the development of beta 2-microglobulin amyloidosis, responsible for nerve tunnel syndromes, arthralgia and chronic joint swelling with frequently multiple subchondral cysts on x-rays. Microcrystalline pathology is dominated by apatite deposits, which may also be involved in the pathogenesis of destructive arthropathy. Articular complications with destruction of the large joints or involvement of the first carpometacarpal joint interfere with the functional prognosis. Sepsis must be excluded in cases of destructive cervical spondyloarthropathies. The pathogenesis of destructive arthropathies is probably multifactorial, consisting of apatite and amyloid deposits, secondary hyperparathyroidism and aluminium poisoning.

Amyloid beta-Peptides↗

[The results of the endoluminal high-dose-rate irradiation of central non-small cell bronchial carcinomas].

Between November 1987 and July 1991 34 patients with a non-small-cell lung cancer were treated with an endobronchial iridium-192 high-dose-rate afterloading therapy. In 13 patients with relapses after percutaneous irradiation brachytherapy was the sole radiotherapy modality with 20 (5 to 29) Gy within 14 (one to 42) days in four (one to six) fractions in a palliative sense. Endoscopically controlled, seven remissions (four complete, three partial) could be achieved. The median duration to local progression was two months, the median survival of this group was nine months. In 21 patients with a medically or surgically unresectable tumor a combined percutaneous (51 [46 to 60] Gy within 4.5 to six weeks) and endobronchial irradiation was done. This patient group consisted of one stage IV, eight stage IIIb, 8 stage IIIa, 1 stage II, 1 stage I patients and two patients with tumor relapses after surgery. Patients were selected for combined therapy by a mostly endo/peribronchial tumor volume. The brachytherapy was applied after an interval of 16 (one to 48) days with 17.5 (9 to 20) Gy in three to four fractions. In 13 patients six to eight weeks after treatment a complete remission by endoscopy was found. Patients with a complete remission had a statistically better survival than the remaining patients. The median estimated survival of this group until local progression was 16 months, the median survival 20 months. In all patients there were two occurrences of hemorrhage (one group I, one group II) and one tracheo-mediastinal fistula (group II), but in no case of these fatal events a local tumor control had been reached. In three patients radiogenic bronchitis occurred up to a degree, which demanded endoscopic interventions. This study suggests, that there might be a subgroup of centrally located lung cancer with endo/peribronchial tumor mass, which gains by a combined radiation treatment with an acceptable risk of side effects. The results should be evaluated in further randomized studies.

Adult↗

[Candida tropicalis arthritis of the shoulder associated with articular chondrocalcinosis].

A case of infection of the scapulohumeral joint following articular infiltrations is reported in a female patient with alcohol-related cirrhosis of the liver. Joint destruction occurred despite appropriate treatment with fluconazole. Candida tropicalis joint infections are seen mainly in immunocompromised hosts and usually cause little destruction of the joint. Most are the result of dissemination via the bloodstream. Preexisting chondrocalcinosis in the patient reported here may have been a contributing factor to the development of extensive joint destruction.

Aged↗

Persistence of B19 parvovirus in synovial membranes of patients with rheumatoid arthritis.

Recent clinical observations support the hypothesis that persistent parvovirus B19 is a triggering factor of rheumatoid arthritis (RA) in certain genetically predisposed individuals. If this hypothesis is correct, a number of RA patients may exhibit parvovirus B19 DNA in their synovial membranes. We tested the synovial tissue and peripheral blood leukocytes of 20 patients with RA, 24 patients with other arthritides or osteoarthritis (non-RA), and 34 healthy blood donors for the presence of parvovirus B19 DNA using specific DNA amplification by polymerase chain reaction (PCR). Using this technique, parvovirus B19 DNA was demonstrated in the synovial biopsies of 75% of patients with RA but in those of only 16.7% of patients with non-RA. In autologous peripheral blood mononuclear cells the percentage of PCR-positive patients was about 15% in both RA and non-RA groups and did not differ from that in healthy controls. When the PCR data were correlated with the presence of anti-parvovirus B19 IgG antibodies in serum and synovia all patients with parvovirus B19 DNA in peripheral blood alone or in both peripheral blood and synovial membrane were seropositive. In contrast, about 40% of patients with parvovirus B19 DNA restricted to the synovial membrane were seronegative. These data indicate a highly disease-related persistence of parvovirus B19 in the rheumatoid synovium.

Antigen-Antibody Reactions↗

[The question of amino acid isomerization in the microwave field. Results of a model study with standard solutions].

Aqueous standard-solutions of L-alanine, L-glutamic acid, and L-proline do not reveal any increase of D-enantiomers after 30 min heating--neither by the conventional method on a hotplate, nor in a standard microwave oven. A specific "microwave effect" and, hence, a special consumer risk is, in contrast to recent assumptions, not detectable. Effects on the amino acids which were observed in conventionally heated samples are explained by higher heat-exposure during the treatment of these samples.

Alanine↗

Sternocostoclavicular hyperostosis: its progression and radiological features. A study of 12 cases.

Twelve cases of sternocostoclavicular hyperostosis were followed up over four to 16 years. The patients underwent repeated radiological examinations of the sternocostoclavicular joints and the sternum, and the extrasternal osseous manifestations of the disease were studied to show changes in the radiological features during long term follow up. Five of 12 (41%) patients had extrasternal manifestations. With the exception of one patient extrasternal manifestations were first detected by scintigraphs because they were asymptomatic. With respect to the sternal manifestations the initial radiological diagnosis was made during an acute phase while painful swelling over the sternum and decreased mobility of the shoulders occurred. The radiological examinations showed the signs of a proliferative destructive arthritis in most patients. In contrast with the frequent occurrences of clinical symptoms, the radiological signs of progression take several years to become detectable. There are no specific bacteriological, serological or histological findings. Usually a permanent increase in the erythrocyte sedimentation rates is found. Sternocostoclavicular hyperostosis is a slowly progressing disease, characterised by a chronic aseptic destructive sternoclavicular arthritis with a reactive low turnover sclerosis that begins in a similar way to an enthesopathy and ends after several decades with total ankylosis. The radiological identification of retrosternal proliferation of soft tissue by computed tomography was found to be a valuable criterion for the differential diagnosis from other benign hyperostotic processes of the sternoclavicular region.

Cervical Vertebrae↗

Determination of cytokines in synovial fluids: correlation with diagnosis and histomorphological characteristics of synovial tissue.

In a study aimed at correlating cytokine levels in synovial fluid with the pathology of rheumatoid arthritis (RA), tumour necrosis factor alpha, interleukin 1 beta and interferon gamma were immunoassayed in 27 patients with RA, 16 patients with other arthritides, 23 with osteoarthritis, 13 patients with trauma, and 18 patients at necropsy without inflammatory disease and not known to have had joint disease (median 27 hours after death). The results for interleukin 1 beta clearly show higher cytokine levels in patients with RA and other arthritides than in patients with osteoarthritis, trauma, or the patients at necropsy. Interferon gamma levels in patients with osteoarthritis and the patients at necropsy, however, were significantly greater than in patients with RA, and tumour necrosis factor alpha levels were also greater in the patients at necropsy compared with patients with RA. This study also correlated histomorphological patterns of synovitis and indicators of local inflammatory activity with synovial fluid cytokine levels, showing, for example, a positive association of interleukin 1 beta titre and a negative association of interferon gamma titre with ulcerogranulomatous synovitis (itself associated with RA). Taken together, these results extend and strengthen data suggesting a possible part played by increased synovial fluid levels of interleukin 1 beta in joint destruction in RA, but provide no evidence for increases in levels of tumour necrosis factor alpha or interferon gamma affecting the disease pathology.

Adult↗

[Destructive arthropathy of the shoulder].

Destructive arthropathy of the shoulder consists of cartilaginous deterioration combined with subchondral osteolysis. The various diseases able to induce joint destruction (infection, neurological disease, chondrocalcinosis, tumour...) are excluded from this description which only concerns the forms with no obvious cause. Since the description of "senile haemorrhagic caries of the shoulder", several authors have reported, under various names, very similar diseases whose common denominator is destruction of the shoulder joint. The pathogenic factors remain unclear, but various theories have been proposed, involving mechanical factors secondary to lesions of the rotator cuff or suggesting the role of apatite microcrystals.

Calcinosis↗

Demonstration of cytomegalovirus (CMV) DNA and anti-CMV response in the synovial membrane and serum of patients with rheumatoid arthritis.

One hundred forty-seven synovial membranes were investigated for the presence of human cytomegalovirus (CMV). In 11 of 83 synovial membranes of patients with rheumatoid arthritis (RA), but only in 2 of 64 synovial membranes from patients with other joint disorders, CMV-DNA could be detected by the polymerase chain reaction (PCR) technique (p less than 0.05). In contrast, the percentage of seropositive patients was not significantly different between the 2 groups of patients and no blood sample from any patient tested revealed the presence of CMV by PCR. Only in patients with RA and CMV positive synovial membranes was the titer of CMV specific antibodies in the synovia higher than in the serum. Thus, the local presence of CMV in the synovial membrane and associated local antiviral responses might participate in the pathogenesis of synovitis in a minority of patients with RA.

Antibodies, Viral↗

[Microcrystal deposit arthropathies of the wrist].

Microcrystalline arthropathies of the wrist include three main forms of microcrystalline pathology: gout, chondrocalcinosis and apatite calcifications. Gout of the wrist is now rare and may be missed, particularly in its chronic form, occasionally associated with tophi and large, often asymmetrical erosions on the X-rays. Chondrocalcinosis is frequent and easy to diagnose in the wrist and may be responsible for a very typical arthropathy predominantly involving the radiocarpal joint, while the frequency and specificity of scapho-trapezoid involvement are controversial. Apatite deposits in the wrist involve various tendons and ligaments, especially the tendon of flexor carpi ulnaris, but may also be responsible for intra-articular pathology.

Apatites↗

[The percutaneous-endocavitary irradiation of esophageal carcinomas].

In a prospective, nonrandomized study 43 patients with inoperable oesophageal carcinoma were treated with a combined therapy of external and intracavitary irradiation according to the Heidelberg protocol adjusted to tumor stage, general condition and age. The proportion of external beam to afterloading doses was 2/3:1/3. The reference doses were between 50 and 75 Gy. Intracavitary radiotherapy was carried out with a HDR-afterloading device in single doses of 5 Gy. In a median follow-up of 23 months 46% had a complete remission and 42% had a partial remission. Within ten months 17 patients (39.5%) showed local tumor progression or recurrence. Presently the estimated median survival time of the whole collective is eleven months. The median survival was significantly influenced by achievement of complete remission (17.7 months in comparison to 8.7 months by missing complete remission). After completion of therapy 90% had sufficient oral nutrition. During long-term follow-up in 44% of the cases repeated measures had to be taken to eliminate initial or recurrent dysphagia. Almost all postradiogenic stenoses were caused by tumor progression. Radiogenic side-effects caused by HDR-afterloading boosts, exceeding the acceptance, were not found. The combined therapy reduces the period of hospitalisation and has the same palliative effects as an exclusively external radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗