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Biomedical subjects

K H Bichler

Publications and source records attributed to K H Bichler.

At least 37 records · Page 2Linked to original sources

Spot urine samples for the metabolic evaluation of urolithiasis patients.

OBJECTIVES: This prospective study was initiated to assess the significance of spot urine specimens (SU) for the metabolic evaluation of stone formers. METHODS: 68 stone patients (51 males, 17 females) and 20 controls (9 males, 11 females) participated. On 3 consecutive days, urine was collected. Fasting (SU1) and postprandial (SU2) SU were obtained. From these, aliquots were taken, all the other urine was mixed to obtain 24-hour timed specimens (24hU). In all specimens, pH, specific gravity, creatinine, calcium, magnesium, phosphate, citrate, uric and oxalic acids were measured. The latter analytes were related to creatinine (mmol/g creatinine). Pearson correlation coefficients with their levels of significance and the day-to-day variation were calculated. Using the values in the control group, normal values (means +/- 2 SD) were established. RESULTS: There was a significant correlation (p < 0.0001) between SU and 24hU for all parameters examined. The day-to-day variation of all analytes was considerable in SU and 24hU. CONCLUSIONS: Despite a minor inaccuracy by relating parameters to creatinine, SU are sufficient in the routine metabolic evaluation of stone formers, since a third of all 24hU has to be rejected because of considerable collection errors. SU circumvent this problem. Because of the day-to-day variation, 3 SU should be obtained to overcome the doubtful significance of one single specimen.

Adolescent↗

[Studies of calcium metabolism in patients with hypercalciuria].

The different subgroups of hypercalciuria cannot be separated clearly by the Pak calcium-load test. To improve the diagnosis and therapy we examined all relevant parameters of calcium metabolism in 32 patients with calcium urolithiasis and hypercalciuria (> 6.25 mmol/day). We also conducted bone mineral density measurements as well as the Pak calcium-load test. In most cases the pathophysiological constellations which Pak takes as the basis for his classification of hypercalciuria could not be shown. To date, diagnostics only insufficiently explains the genesis of hypercalciuria (except pHPT). As a consequence, a therapeutic problem arises: a low-calcium diet should not be generally recommended, since some patients may develop osteopenia. From our investigation the following diagnostic and therapeutic conclusions can be drawn: (1) Hypercalciuria in primary hyperparathyroidism should be treated by surgical removal of the adenoma. (2) The parathormone-independent osteogenic form should be treated with thiazides. (3) Hypercalciuria with increased 1.25-dihydroxyvitamin D should be treated by low-calcium diet.

Adult↗

Investigations on bone metabolism of urological tumors forming metastases.

Bone metastases of urological tumors occur in nearly 40% of all primary tumors of the prostate, the kidney and the bladder. The quality of metastases may be described as osteolytic, osteoplastic or mixed lesion. Whereas prostate cancers produce mainly osteoplastic lesions, renal cell carcinomas predominantly generate osteolytic lesions. In bladder cancer both forms of metastases occur in tantamount numbers. However, diagnostics still presents many difficulties, since it is not feasible to identify very small metastases until symptoms have manifested themselves. The purpose of our study was to evaluate measurement technique and classification of significant serum markers for monitoring the course of disease. Patients with primary urological tumors and metastases in the skeleton were investigated and compared with healthy volunteers. Osteodensitometry was used to confirm and to replace radiological diagnosis of bone metastases. Thus it was possible to locate the extent and obtain information on the maximum charge and the stability of metastases. Our examinations revealed that distinct serum markers describe the changes in bone evoked by metastases. In comparison with healthy volunteers, patients with osteoplastic lesions and osteolytic lesions showed increases in hydroxproline and pyridinium crosslinks (significance at least p < 0.005). Osteocalcin was elevated only in osteoplastic lesions versus healthy volunteers (p < 0.01). For diagnostics of osteoplastic and osteolytic metastases, either alkaline phosphatase or the skeleton-specific phosphatase (ostase) can be measured serologically. Both parameters showed significant elevation in the patient groups when set against the healthy controls (both p < 0.0001). Compared with lytic lesions osteoplastic carcinomas revealed significant increase of alkaline phosphatase (p < 0.0001) and osteocalcin (p < 0.005). In examination of bone metabolism in patients with skeletal metastases the following parameters are of eminent interest: osteocalcin, hydroxyproline or pyridinium crosslinks, alkaline phosphatase or ostase. These serological parameters could be helpful even with regard to early diagnosis of bone metastases. Evaluation of measuring techniques suggests quantifying pyridinium crosslinks instead of hydroxyproline, because they may be assessed without taking the patient's diet into account. Determination of bone density may be helpful in diagnostics or control of therapy modalities.

Adult↗

Osteocalcin response to calcium-restricted diet: a helpful tool for the workup of hypercalciuria.

OBJECTIVES: The treatment of hypercalciuria is controversial. This study investigated whether the osteocalcin response (OCR) to a calcium-restricted diet is a potential tool for the differential therapy of hypercalciuria. 56 patients with calcium urolithiasis were investigated. METHODS: Osteocalcin (OC) was measured on a free diet (OC 1) and after a calcium-restricted diet (400 mg/24 h for 1 week, OC 2). The OCR was expressed as 100 x (OC 2 - OC 1)/OC 1. A calcium load test and vertebral mineral density measurements (L2-L4) were performed additionally. RESULTS: 27 patients showed diet-dependent hypercalciuria, 15 of them being classified as absorptive hypercalciuria type II (AH II). 12 were normocalciuric (NC). 29 patients had diet-independent hypercalciuria, 22 being classified as renal hypercalciuria (RH), 7 as absorptive hypercalciuria type I (AH I). 22 patients (42%) showed a positive OCR, indicating an increased bone turnover. Vertebral mineral density was lower in patients with positive than with negative OCR. Generally patients with RH or NC showed a positive OCR, patients with AH a negative or no OCR. 2 patients with AH, however, showed highly positive OCR, indicating negative calcium balance. Long-term follow-up on a low calcium diet showed a steady decrease in bone mineral density. CONCLUSIONS: This demonstrates that the OCR is more reliable to determine the appropriate management of hypercalciuria than calcium load tests. For practical purposes, we suggest treating hypercalciuric patients with positive OCR with thiazides; diet-dependent hypercalciuria with negative OCR should be treated with a low calcium diet.

Absorptiometry, Photon↗

Combined endoscopic closure of rectourethral fistula.

PURPOSE: Rectourethral fistula formation is a rare complication of radical prostatectomy and other pelvic surgical procedures. MATERIALS AND METHODS: In 2 patients endoscopic closure of the fistula was performed by combined transrectal endoscopic excision of the fistula, endoscopic suture, and simultaneous transurethral fulguration and fibrin application. RESULTS: This combined approach resulted in closure of the fistula in both patients as proved by rectoscopy, retrograde urethrography and disappearance of all clinical symptoms. The latest postoperative followup was 18 months. CONCLUSIONS: Any open procedure to correct a rectourethral fistula is considered major surgery. Therefore, the minimally invasive approach described should be attempted first in patients with a small rectourethral fistula.

Aged↗

Effects of extracorporeal shock wave lithotripsy on plasma concentrations of endothelin and renin in humans.

PURPOSE: There is ongoing controversy regarding blood pressure changes after extracorporeal shock wave lithotripsy (ESWL*). Experimental data suggest a role for renin but only few data are relevant to humans. It has been shown that renin secretion is stimulated by endothelin, a recently discovered peptide with strong vasoconstrictive properties and stimulating effects on renin secretion. Endothelin is relevant in the development of hypertension and acute renal failure. MATERIALS AND METHODS: In a prospective study of 48 normotensive patients undergoing ESWL for renal stones the influence of high energy shock waves on plasma endothelin and active renin was analyzed. These substances are secreted by renal cells in response to hemodynamic alterations, and inflammatory and traumatic processes. Peripheral blood samples were analyzed for active renin and endothelin before, and immediately, 1, 3 and 5 days after ESWL. Blood pressure was measured before, and 1, 3 and 5 days after ESWL. RESULTS: Only a slight and transient increase was noted in active renin, which was in the same range as that found after mental stress. Endothelin and blood pressure were not significantly influenced by ESWL. There was no correlation between endothelin and active renin. Thus, the increase in active renin was not mediated by endothelin. CONCLUSIONS: The transient increase in active renin cannot be attributed to the development of hypertension. The lack of influence of ESWL on endothelin indicates that ESWL, at least in the routine clinical setting, does not cause severe renal trauma.

Blood Pressure↗

[Results of color-coded duplex ultrasound diagnosis (angiodynography) after intraurethral administration of PgE1 in erectile dysfunction].

When the pathomechanism of erectile dysfunction is obscure, intraurethral administration of prostaglandin E1 is followed by a marked increase in blood flow velocity in the penile arteries as measured by color-coded Duplex sonography. This increase compares to that following intracavernous administration of half the dose of prostaglandin E1. The difference in the effects after intraurethral and intracavernous administration is the missing rigidity after intraurethral application; there must be a loss of pharmacological efficacy to the smooth penile muscles. Clinical efficacy is to be expected with higher intraurethral dosage.

Adult↗

[The significance of citrate, uromucoid and GAG for diagnosis of renal tubular acidosis in patients with urinary calculi].

Renal tubular acidosis (type I) is characterized by alterations that lead to disturbed acidification in the tubule. As a result of these alterations, the excretion of uromucoid (formed in the distal tubule), citrate and glycosaminoglycan (GAG) is considerably reduced. There have been numerous investigations on changes in urine pH, citrate and calcium, but few, if any studies on the excretion of uromucoid and GAG. Apart from calcium, phosphate, pH and urease, the present study investigated the excretion of uromucoid, citrate and GAG in a collective of 41 stone patients with renal tubular acidosis (type I). We found that uromucoid excretion was reduced on 90.5%, GAG in 72.2% and citrate in 96% of cases. The reduction of uromucoid excretion in particular is characteristic of RTA I, and it has the function of a marker.

Acidosis, Renal Tubular↗

Reduction of vitamin D induced stone formation by calcium.

Investigations were carried out as to whether cytoprotective agents such as calcium antagonists can influence vitamin D induced nephrolithiasis. Increased vitamin D levels are found in 10-30% of all calcium oxalate stone formers. Male rats were assigned to one of the following groups: (1) 1,25-dihydroxycholecalciferol (DHCC) (n = 8), (2) 1,25-DHCC + calcium antagonist Goe 6070 (a new 1,4-dihydronaphthyridine, Goedecke, Berlin) (n = 8), or (3) control (n = 8). 1,25-DHCC was administered for 6 days (120 pmol/24 h s.c.), Goe 6070 (1 mg/kg/24 h) by gavage. Clearance studies were performed on day 6. Kidneys were taken for histological examination and determination of calcium tissue content. 1,25-DHCC induced substantial concrement formation, which could be significantly limited by Goe 6070. The calcium tissue content was also reduced (0.17 vs. 0.04 mg/100 mg dry weight). 1,25-DHCC induced a dramatic fall in the glomerular filtration rate (GFR) (3.84 ml/min per kilogram). This reduction could be almost completely inhibited by the concomitant application of Goe 6070 (9.4 ml/min per kilogram; control 10.7 ml/min per kilogram). Goe 6070 did not influence the calcium handling. The results demonstrate a protective effect of Goe 6070 on vitamin D induced nephrolithias. The histological pattern (intracellular and membrane-bound concretions) and the fact that biochemical parameters were not influenced significantly by Goe 6070 indicate that cellular proceses are important for 1,25-DHCC-induced nephrolithiasis.

Animals↗

Verapamil limits shockwave-induced renal tubular damage in vivo.

Previous investigations on Madin Darby Canine Kidney (MDCK) cells demonstrated the protective effect of verapamil against shockwave-induced tubular dysfunction. In the present study, we investigated whether verapamil is also protective against shockwave-induced damage in vivo. Male rates were randomly assigned to three groups: verapamil (N = 18) (Group I), control (N = 18) (Group II), or sham treatment (N = 4) (Group III). Groups I and II were treated with 500 shockwaves to each kidney with the Dornier MFL 5000 at 18 kV. Animals assigned to Group III received only anesthesics. Verapamil was given to the animals in Group I for 5 days starting 1 day before shockwave exposure. Urine was collected for 8 hours the day before and immediately, 1.7, and 28 days after shockwave exposure (SWE) for measurement of volume, osmolality, hemoglobin, protein, N-acetyl-beta-glucosaminidase (NAG), beta 2-microglobulin (beta 2M), sodium, and creatinine. Kidneys were perfused and removed for histologic study 1, 7, and 28 days after SWE in six animals of Groups I and II. Blood was taken in these rats (Day 1 after SWE) for the determination of creatinine and sodium and the calculation of the creatinine clearance (CCr) and the fractional excretion of sodium (FENa). After SWE, there was strong diuresis and significantly increased excretion of NAG and beta 2M in the controls, while urine osmolality decreased. These changes were significantly less pronounced in the verapamil-treated rats. The CCr was higher and FENa lower than in the latter group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Limitation of shock-wave-induced renal tubular dysfunction by nifedipine.

In a prospective randomized study, the effects of the calcium entry blocker nifedipine on shock-wave-induced tubular impairment were studied. 24 patients with renal pelvic or calyceal stones undergoing anesthesia-free extra-corporeal shock wave lithotripsy (ESWL) without ancillary measures were randomly assigned to the nifedipine group (n = 12) or the control group (n = 12). Four doses of nifedipine (10 mg t.i.d.) were given orally, starting the night before ESWL. Controls received no medication. To assess renal tubular function, the urinary excretion of alpha 1-microglobulin (A1M), N-acetyl-beta-glucosaminidase (NAG) and Tamm-Horsfall protein (THP) were measured before, immediately, 12 and 24 h after ESWL. After lithotripsy, there was a rise in urinary A1M and NAG which was significantly higher in the control than in the nifedipine group. THP, a glycoprotein synthesized by distal tubular cells, fell significantly less in the nifedipine group compared to the controls. Our results indicate that nifedipine exhibits a protective effect on shock-wave-induced tubular damage similar to verapamil. The underlying mechanisms are not clarified yet, direct actions on tubular cells and interference with renal hemodynamics have to be discussed.

Acetylglucosaminidase↗

Protective effect of verapamil on shock wave induced renal tubular dysfunction.

In a prospective randomized study, the effects of the calcium entry blocker verapamil on shock wave induced tubular impairment were examined. A total of 24 patients with renal pelvis or caliceal stones undergoing anesthesia-free extracorporeal shock wave lithotripsy (ESWL*) without auxiliary measures was randomly assigned to the verapamil group (12) or the control group (12). Four doses of verapamil (80 mg. each) were given orally starting the night before ESWL. Controls received no medication. To assess renal tubular function the urinary excretion of alpha 1-microglobulin, N-acetyl-beta-glucosaminidase and Tamm-Horsfall protein were determined before, immediately, and 12 and 24 hours after ESWL. After ESWL there was an increase in urinary alpha 1-microglobulin and N-acetyl-beta-glucosaminidase, which was significantly higher in the control than in the verapamil group. Tamm-Horsfall protein, a glycoprotein synthesized by the distal tubules, decreased significantly less in the verapamil group compared to the controls. Our results indicate that verapamil exhibits a protective effect on shock wave induced tubular damage. The underlying mechanisms are not elucidated yet, and direct actions on tubular cells and interference with renal hemodynamics are to be discussed.

Acetylglucosaminidase↗

Evaluation of the acute scrotum by color-coded Doppler ultrasonography.

Color-coded Doppler ultrasonography is a combination of real-time sonography and duplex sonography for noninvasive imaging of arterial and venous blood vessels. In 40 patients with acute onset of scrotal pain this diagnostic procedure was correlated with the findings at surgical exploration: 11 had testicular torsion, 4 hydatid torsion, 13 spontaneous detorsion, 2 blunt scrotal trauma and 10 epididymitis. For testicular torsion color-coded Doppler ultrasonography had a sensitivity of 82% and a specificity of 100%, and for epididymitis the sensitivity was 70% and specificity was 88%. Color-coded ultrasonography readily demonstrates testicular perfusion. In cases of incomplete or early torsion some residual perfusion may be detected leading to false-negative results. Despite this fact, color-coded Doppler ultrasonography currently is the most valuable diagnostic modality in the evaluation of the acute scrotum.

Acute Disease↗

New trends in the treatment of benign prostatic hyperplasia and carcinoma of the prostate.

Benign prostatic hyperplasia (BPH) is a very common condition affecting over 800,000 American males each year. A standard, effective, and well-proven therapy is prostatectomy. This surgical procedure is used to treat, in the United States, approximately 400,000 BPH patients annually. Major treatment benefit is expected in 70% to 80% of patients. Complications are seen in 20% of the surgically treated patients. Due to the advanced age of BPH patients and the presence of other serious coexisting medical problems, surgical therapy may be difficult to utilize. These patients, who present a high risk for surgery, are in need of alternative treatments. Alternative therapy in BPH patients with clinically important symptoms and signs of urinary outflow obstruction include treatment with pharmacological agents, balloon dilatation, laser beam therapy, transurethral thermal therapy, transrectal microwave hyperthermia, and transurethral microwave hyperthermia. These alternative treatment modalities are currently under intensive study. These new treatment modalities ultimately must be compared with the standard treatment, which is prostatectomy. Due to the unpredictable natural history of BPH, it is desirable that each Phase III study should contain a no-treatment observation-only arm. Adenocarcinoma of the prostate (CaP) has become a tumor, which first in frequency, and second in importance in cancer mortality statistics of American males. Local tumor control rates and long-term survivals, with radical prostatectomy or radiation therapy, have been excellent. There was, however, recent concern regarding a high incidence of microscopic local tumor recurrence following a definitive course of irradiation. Deep regional or intracavitary hyperthermia (HT) with phase steering may be of value as an adjuvant treatment to radiotherapy. This HT may increase the incidence of local tumor control obtained with radiotherapy. Phase I-II clinical studies are currently underway.

Adrenergic alpha-Antagonists↗

Influence of immunotherapy (IL2 + LAK + inhibition of prostaglandin synthesis) on peripheral blood immune parameters and in vitro cytokine production in metastatic renal cell carcinoma.

Previous results on the peripheral blood immune status of renal cell carcinoma had indicated immunosuppression in metastatic disease, possibly mediated by prostaglandin E2 (PGE2). In the present study the immunologic effects of inhibition of PG synthesis by piroxicam in combination with interleukin 2 (IL 2) + lymphokine-activated killer (LAK) cell therapy were tested by immunomonitoring. In addition to peripheral blood parameters (lymphocyte subpopulations, neopterin, beta 2-microglobulin, TNF, IL 1, IFN gamma) we recorded in vitro cellular activity by incubating the patients' peripheral blood mononuclear cells (PBMC) in media containing fetal calf serum (FCS) or autologous serum, and either IL 2 or buffer. After 24 h of incubation we measured PGE2 and cytokine levels in supernatants. Systemic application of IL 2 induced in vivo lymphocyte proliferation and clearly influenced the serum levels of neopterin, beta 2-microglobulin and TNF. There was minor affection of IFN gamma and none of IL 1. PBMC in vitro produced high amounts of PGE2, IL 1 and TNF pretherapeutically, during therapy in vitro synthesis of these parameters decreased. Consistent production of IFN gamma was detected in supernatants only when FCS and IL 2 were added to the medium. Lack of affection of IFN gamma production in the autologous system during therapy indicated impaired cellular activity, which could neither be improved by therapy of the patient using IL 2 nor by adding IL 2 to the culture medium. Immunosuppression seems to interfere in a complex way with immunotherapy. Therapeutical influence of immunosuppression based on the results of immunomonitoring, however, seems to be a promising strategy for improving the still limited clinical results of immunotherapy.

Adult↗

Influence of transrectal hyperthermia on prostate-specific antigen in prostatic cancer and benign prostatic hyperplasia.

The prostate-specific antigen (PSA) is a glycoprotein synthesized exclusively by the prostate. Since manipulations on the prostate can increase PSA serum levels, we investigated the effects of transrectal hyperthermia on PSA levels in prostate cancer (PC) and benign prostatic hyperplasia (BPH). Patients and treatments were the following: group 1a, PC St.D (n = 12): 8 hyperthermia sessions (twice a week) and LHRH-agonists plus flutamide; group 1b, PC St.D (hormone resistant; n = 10): 8 hyperthermia sessions (once a week) and epirubicin (50 mg intravenously, once a week); group 1c, PC St.C (n = 5): 6 hyperthermia sessions (once a week) and radiotherapy (60 Gy); group 2, BPH (n = 10): 8 sessions (twice a week). PSA levels were determined before, during (immediately before each hyperthermia session) and 1 week after therapy. Apart from hormone-/hyperthermia-treated patients, who showed a continuous decrease in PSA during therapy, all the other groups revealed a transient increase in PSA during the hyperthermia treatment. This effect is attributed to manipulations on the prostate and hyperthermia-specific effects on prostatic cells. The decrease in PSA on hormone/hyperthermia therapy can be explained by the tremendous effect of androgen deprivation on PSA levels overshadowing the hyperthermia effect.

Aged↗

[Methodologic comparison of the analysis of urinary calculi. Roentgen diffractometry, polarization microscopy and microscopic-microchemical component analysis].

Not only instrumental, apparative or operative stone extraction is necessary for patients with urolithiasis (particularly those with recurrent urolithiasis); preventive treatment is also called for, and for this exact analysis of the composition of the stones is essential. The procedures currently accepted as standard for stone analysis are: X-ray diffraction, infrared spectroscopy, polarisation microscopy and the complicated chemico-quantitative analyses performed in some institutes. Recently a new, so-called microscopic-microchemical, analysis of stone components has been presented (the Harzalith). To test the value of this procedure as compared to e.g. X-ray diffraction or polarization microscopy, a comparative study was carried out in our department. Thirty different urolith compositions (calculi with one and with more components) were analysed qualitatively and quantitatively by three methods. No qualitative difference was found between X-ray diffraction and polarization microscopy; however, there was a difference from the Harzalith method, and with increasing number of components there was hardly any correspondence with the other methods. Only 10% of the calculi with three or four components could be analysed correctly. Often, too many components were determined by the new method. The test material was analysed by three laboratory assistants working independently of each other.

Cholelithiasis↗