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Biomedical subjects

R Hartung

Publications and source records attributed to R Hartung.

At least 19 recordsLinked to original sources

Biomodulation of 5-Fu cytotoxicity by folinic acid and its stereoisomers: in vitro experiments with different cell lines of prostatic cancer.

The results of cytotoxic chemotherapy for advanced, hormone-escaped prostate cancer have been disappointing. Evaluation of the effect of new drugs or new combinations with already known ones is required. The antimetabolite 5-fluorouracil (5-FU) has been shown to be active in prostate cancer, acting via inhibition of thymidylate synthase, an essential enzyme in DNA de novo synthesis. Experiments with cell lines of different tumors have shown that 5-FU activity can be modulated by addition of the coenzyme tetrahydrofolic acid (folinic acid). We investigated the effect of folinic acid and its stereoisomers on 5-FU action in different cell lines of prostate cancer. It was found that addition of non-toxic folinic acid led to a two- to fourfold better antiproliferative effect of 5-FU. The unnatural 6R isomer, which is a compound of chemically synthesized folinic acid, inhibited the modulatory effect of the natural 6S isomer. Our results indicated that a combination of folinic acid and 5-FU may result in a better response of patients with hormone-resistant prostate cancer than of patients treated with 5-FU alone.

Antineoplastic Agents

No association of converting enzyme insertion/deletion polymorphism with immunoglobulin A glomerulonephritis.

It has been recently reported that in type 1 diabetes the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme gene is associated with the presence of diabetic nephropathy. Tissue angiotensin I-converting enzyme is determined by I/D polymorphism, and it has been speculated that in diabetes differences of local angiotensin II availability determine the risk of renal disease. Since angiotensin II is thought to play an important role in the evolution of renal disease in general, we tested whether genotype distribution of the I/D polymorphism is also different in patients with immunoglobulin A-glomerulonephritis (IgA-GN). Furthermore we compared IgA-GN patients with (1) stable renal function or (2) terminal renal failure to investigate a potential role of the I/D polymorphism in the renal prognosis. We examined 122 patients with biopsy-confirmed IgA-GN who had stable renal function and 82 dialysis-dependent or transplanted patients with biopsy-confirmed IgA-GN. Furthermore, in 134 healthy individuals used as controls we analyzed the DNA for normal distribution of genotypes and allele frequencies. The polymorphic region was amplified using polymerase chain reaction with specific primers. Alleles were detected on 2% agarose gels. Genotype distributions and allele frequencies were not significantly different between controls and patients with IgA-GN and stable renal function. Furthermore, no significant difference in genotype distribution was detected between patients with IgA-GN and stable renal function compared with patients with IgA-GN and end-stage renal failure, although a trend for a higher frequency of DD-homozygotes was noted in the latter group (P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Negotiating ureteral stenoses and kinks with a hydrophilic wire.

Negotiating a tortuous or obstructed ureter with a wire can be time-consuming and sometimes tiring. The principle of using a slippery floppy wire and then replacing it with a stiff wire through a 5-french open-ended ureteral catheter yields a high success rate. The ureteral catheter can be used for a radiocontrast study and allows access for a 0.035 'coaxial wire', which can be used as a guide wire for a single or double J stent.

Humans

Prostate-specific antigen density and age-specific prostate-specific antigen values: the solution of prostate cancer screening?

The results of 225 systematic prostate biopsies from 1992 to 1993 were evaluated retrospectively. The parameters prostate-specific antigen (PSA) density and age-specific PSA values were compared with digital rectal examination, transrectal ultrasound, and PSA as single parameters and possible combinations. The PSA density proved to have the highest specificity of all single parameters, but the sensitivity was low. Age-specific PSA values are offering a good compromise of sensitivity and specificity as compared with fixed cutoff levels. Since there is no sufficient screening parameter up to now, a combination of all parameters is recommended for screening of early prostate cancer.

Aged

Transurethral prostatectomy (TURP): still the gold standard?

1. The indication for treating BPH can be established very precisely today. It is important to select the alternative procedures with a good workup for individual therapy. 2. A large volume prostate with proven obstruction is an indication for TURP or open prostatectomy, still the best choice of treatment with the best longterm results concerning all obstructive parameters. In future there may be less surgery due to the other possibilities but teaching and handling the gold standard should not be forgotten in using alternative techniques. 3. Especially for high risk patients there are minimal invasive methods so that a permanent catheter in a patient should be an exception. 4. Also with new medications we expect better results. Prostate selective alpha-blockers and reduction inhibitors probably also in combination of both may be sufficient therapy for many patients. It has to be examined whether minimal invasive instrumental treatments like transurethral thermotherapy can be compared with medication. The most important result of the discussion in the last years was improving the clinical workup for finding the indication for surgery. Too many new instrumental methods appeared at the same time and we are in a period of selection and investigation to know which technique can be compared with the gold standard of TURP. Also in using minimal invasive therapy the indication must be very clear because also the new techniques are not totally free from complications.

Catheterization

Prostate-specific antigen in urine.

We investigated concentrations of prostate-specific antigen (PSA) in mid-stream urine of 213 patients. Among them were 34 females. Diagnoses of the male patients were 42 benign prostatic hypertrophy (BPH), 21 localized prostate cancer prior to radical prostatectomy (RP), 15 post-RP without distant or local recurrence, 5 post-RP with local recurrence and 82 with other urological diseases. PSA levels were determined by the Hybritech Tandem E method. Female urine samples were positive in 38% of the cases. This and the finding of PSA in urine of men after RP is most likely due to extraprostatic production by periurethral glands. Urinary PSA levels do not differ between patients with BPH, organ-confined prostate cancer and other diagnoses. In some cases, however, urine PSA levels can be elevated in men with local tumor recurrence after RP when serum levels are still undetectably low. This indicates that the determination of urinary PSA concentration might be useful in the follow-up of patients after RP.

Biomarkers, Tumor

Detection of somatic changes in human renal cell carcinomas with oligonucleotide probes specific for simple repeat motifs.

The purpose of our study was to detect somatic changes in renal cell carcinoma by multilocus fingerprinting. DNA fingerprints were generated from the DNA of normal and malignant renal tissue samples of 29 patients with nonhereditary kidney carcinoma by using oligonucleotide probes specific for simple repeat motifs such as (GTG)5, (CA)8, (GACA)4, or (TTAGGG)3. Each probe rendered a typical fingerprint pattern, because it is specific with respect to the target regions recognized in the genome. The restriction enzymes used were HinfI and HaeIII. Changed banding patterns were detected by using (GTG)5 in 20% of the tumors, in 20% for (CA)8 after HinfI digestion, and in 10% after HaeIII digestion. Even more informative probes were (GACA)4, showing 70% changes after HaeIII digestion, and (TTAGGG)3, with 80% changes after digestion with either enzyme. Since the simple repeat motifs recognized by (GACA)4 are localized on the short arms of the acrocentric chromosomes (13, 14, 15, 21, and 22), it is possible that sequences important for renal carcinogenesis are present in these regions. The observation of changes in regions to which (TTAGGG)3 hybridizes points to an involvement of DNA elements in telomeric sequence related regions in human kidney tumor formation.

Adult

Modulation of in vitro cell growth of human and murine urothelial tumor cell lines under the influence of interleukin-3, granulocyte-, macrophage- and granulocyte-colony-stimulating factor.

To elucidate possible growth-modulating effects of interleukin 3 (IL-3), granulocyte-macrophage-colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF), human transitional cell carcinoma (TCC) cell lines T24, RT112, EJ and 647 V were solitarily and continuously exposed to these hematopoietic growth factors at concentrations of 1-100 ng/ml. The murine line MBT-2 was used as a negative and the colon carcinoma cell line HTB38 as a positive control, because of species specificity and known proliferation in response to growth factors, respectively. In the T24 TCC-line solitary and continuous exposure to IL-3, GM-CSF and G-CSF at the highest concentration of 100 ng/ml led to a significant proliferation of cell growth in vitro. Significant proliferation in the RT112 line was only achieved with continuous exposure to IL-3 and GM-CSF (100 ng/ml); G-CSF failed to induce growth modulation in the RT112 line. No significant proliferative effect of any of cytokines administered was observed in the 647V line. Exposure of the EJ line to cytokines at the highest activity levels had a proliferative effect only in suboptimal growth conditions.

Adenocarcinoma

Adenosine triphosphate and adenosine diphosphate in human semen: correlation with sperm count and motility.

Adenosine triphosphate (ATP) and adenosine diphosphate (ADP) have been correlated with traditional semen parameters such as forward motility and sperm count. ATP and ADP were determined by a bioluminescence assay using the luciferin-luciferase reaction. Short boiling of the ejaculate was performed to inactivate phosphatases (ATPases) in the seminal plasma and the sperm tails. Fresh and deep-frozen semen samples from 45 men with oligozoospermia (n = 22) and normal sperm count (n = 23) were evaluated. Freezing of the sperm for 12 weeks did not effect the ATP or ADP content in the spermatozoa as compared to fresh semen. ATP and ADP concentration was in the range of picomoles/microliter and showed a significant correlation with the number of normal sperm per milliliter and a less marked correlation with the sperm motility. ATP and ADP concentration in the spermatozoa can be measured relatively easy and is reproducible. Unlike the monotonous evaluation of sperm motility by a technician, this biochemical method provides an objective parameter for semen quality. These qualities suggest that this method could be a way to determine the fertilizing potential of semen and to relate this to actual pregnancy rates.

Adenosine Diphosphate

Implantation metastasis after a suprapubic catheter in a case of bladder cancer.

We report about a patient who was treated with a percutaneous suprapubic cystostomy in order to relieve repeated urinary retention. Two hours later a bladder tumor was found and the suprapubic catheter was removed. After transurethral resection of the bladder tumor the histological specimen showed a pT3 G3 squamous cell carcinoma. Because of the age and reduced performance status of the patient a radical cystectomy was contraindicated. In a second approach we performed again a transurethral resection of the bladder tumor simultaneously with a resection of the prostate. Eight weeks later the patient was admitted to our hospital because of reduced performance status and gross haematuria. We found a widespread bladder tumor with an implantation metastasis in the abdominal wall at the site where the suprapubic catheter was placed and multiple lung metastases. The patient died within one week after admission. The literature is reviewed and therapeutic strategies are discussed.

Aged

Effect of digital rectal examination on serum concentration of prostate-specific antigen.

Prostate-specific antigen (PSA) is used for screening and follow-up of patients with prostate cancer. The effect of certain diagnostic procedures on PSA serum levels is not well defined. Therefore, the effect of digital rectal examination (DRE) on PSA serum levels was investigated. No significant difference was observed in PSA values before and after DRE when blood samples were taken 1-3 min after palpation of the prostate. Kinetic studies demonstrated a significant increase in PSA values up to the factor 3.2 in 14 of 19 patients 2-6 h after DRE. In 9 of 14 cases, PSA was within the initial range 24 h after DRE. That means that a urologist is allowed to take blood samples for the determination of PSA at least within 3 min after palpating a suspicious prostate without getting false-positive results.

Aged

Patterns of ploidy in renal cell carcinoma.

In a prospective study the patterns of ploidy in 119 kidneys from patients with renal cell carcinoma were analyzed by flow cytometry. A rate of DNA aneuploidy of 53% was observed in the investigated tumors. However, in 4% of the kidneys aneuploid cell distributions were also proven in macroscopically intact tissue far away from the tumor. Although we do not know at present, if these were benign, premalignant or malignant cell alterations, this observation should be considered for decisions regarding conservative renal surgery.

Aneuploidy