Gene expression profiles of human proximal tubular epithelial cells in proteinuric nephropathies.

In kidney disease renal proximal tubular epithelial cells (RPTEC) actively contribute to the progression of tubulointerstitial fibrosis by mediating both an inflammatory response and via epithelial-to-mesenchymal transition. Using laser capture microdissection we specifically isolated RPTEC from cryosections of the healthy parts of kidneys removed owing to renal cell carcinoma and from kidney biopsies from patients with proteinuric nephropathies. RNA was extracted and hybridized to complementary DNA microarrays after linear RNA amplification. Statistical analysis identified 168 unique genes with known gene ontology association, which separated patients from controls. Besides distinct alterations in signal-transduction pathways (e.g. Wnt signalling), functional annotation revealed a significant upregulation of genes involved in cell proliferation and cell cycle control (like insulin-like growth factor 1 or cell division cycle 34), cell differentiation (e.g. bone morphogenetic protein 7), immune response, intracellular transport and metabolism in RPTEC from patients. On the contrary we found differential expression of a number of genes responsible for cell adhesion (like BH-protocadherin) with a marked downregulation of most of these transcripts. In summary, our results obtained from RPTEC revealed a differential regulation of genes, which are likely to be involved in either pro-fibrotic or tubulo-protective mechanisms in proteinuric patients at an early stage of kidney disease.

Loss of cytokeratin expression and formation of actin stress fibers in dedifferentiated MDCK-C7 cell lines.

MDCK-C7 cells dedifferentiated either by transient alkaline stress (C7F cells) or by transfection with a constitutively active mutant of the mitogen-activated protein kinase kinase MEK1 (C7caMEK1 cells) were analyzed by western blot and immunofluorescence microscopy to compare the expression of different cytokeratins, vimentin, and alpha-smooth muscle actin. Expression of all cytokeratins tested, the type II-neutral and basic cytokeratins CK5, CK7, CK8 as well as the type I-acidic keratins CK17 and CK19, was substantially reduced in dedifferentiated cell lines C7F and C7caMEK1 when compared with epithelial wild-type MDCK-C7 cells or mock-transfected MDCK-C7 cells. While vimentin expression was detected in all of the four MDCK-C7 cell lines examined, only the dedifferentiated cell lines C7F and C7caMEK1, which have been reported to express highly active ERK2, exhibited formation of alpha-smooth muscle actin-containing stress fibers. Taken together our results show that, associated with an increase in ERK2 activity, an epithelial to mesenchymal dedifferentiation occurred in both MDCK-C7F cells and caMEK1-transfected MDCK-C7 cells.

Developmentally delayed children: effects on the normal sibling.

The experience of having a sibling is common for most children. What happens to a child when a sibling is developmentally delayed or disabled? What can parents do to improve the adjustment of their nondelayed child?

Extracorporeal shock wave lithotripsy for large renal stones. To what size is extracorporeal shock wave lithotripsy alone feasible?

The complications after extracorporeal shock wave lithotripsy (ESWL) for large renal calculi could be reduced by insertion of ureteral stents. In a prospective study, the critical stone size for ESWL combined with ureteral stenting was looked for. Sixty consecutive patients entered the study, 17 patients suffered from renal calculi with a length of greater than 4 cm and a width of greater than 3 cm (group 1), and in 43 patients the calculi measured between 4 x 3 and 2.5 x 1.5 cm2 (group 2). ESWL was performed with the Dornier apparatus HM-3. A ureteral stent was placed immediately before ESWL. In group 1 with very large stones, significantly more obstructive problems were encountered. Three months after ESWL, only 6 of 14 (43%) were free of stones or with stone material likely to discharge spontaneously. In group 2, a success rate of 25 of 29 (86%) was noticed, which was considered satisfactory. For most stones greater than 4 x 3 cm2 the combination of percutaneous nephrolithotomy and ESWL seems to be the preferred treatment.

Bilateral testicular germ cell tumors: a report of 20 cases.

Of 412 patients with unilateral testicular cancer 20 (4.3 per cent) suffered a second primary germ cell tumor: 1 had a simultaneous bilateral tumor and in the remaining 19 the second tumor was diagnosed after an interval of 2 months to 32 years. Patients with clinical stages III and IV disease were found only in the group with a second tumor. In 5 patients known risk factors for the development of testicular tumors were found and in 2 prior testicular biopsies showed carcinoma in situ. Effective chemotherapy was used more often in the treatment of the second primary tumor. Of the 20 patients 18 (90 per cent) are free of disease after a mean observation of 5.7 years. A long followup of testicular cancer patients with sonographic evaluation of the remaining testis as well as periodic self-examination by the patient is required.

[Value of microhematuria, urine cytology, TPA and neopterin in the after care of patients with bladder tumors]. / Der Wert Mikrohämaturie, Harnzytologie, TPA und Neopterin in der Nachsorge von Blasentumorpatienten.

Tumor recurrences were observed 70 times in 715 cystoscopies performed in 253 patients. The sensitivity of microhematuria to detect a tumor recurrence was 61%, the specificity 84%. The sensitivity of microhematuria increased to 90% in Tis and T2 tumors. Urine cytology showed a specificity of 100% and a sensitivity of only 43%. The specificity and sensitivity of TPA was only 58% and 41%, respectively, the latter increased to 80% in Tis. 60 patients with proven tumor recurrence showed an increase of neopterin with higher tumor stage. In tumors of stage T2 and Tis serum neopterin was raised in 90% and urine neopterin in 75%. Based on these results cystoscopy, exfoliative urinary cytology and urine analysis are obligatory in the follow-up of patients with superficial bladder cancer. Because of the low specificity (29-41%) TPA and neopterin are not suitable for follow-up.

[Experiences in the treatment of advanced nonseminomatous testicular tumor]. / Erfahrungen in der Behandlung des fortgeschrittenen nichtseminomatösen Hodentumors.

48 patients with nonseminomatous testicular tumours were treated between 1980 and 1984. 19 patients had bulky stage II c or disseminated disease; according the Royal Marsden staging classification 5 patients had stage II c, 2 patients III and 12 patients stage IV. The pT stage of the primary tumour showed no correlation to low stage disease, but pT was only found in advanced disease. In disseminated disease histological examination revealed more cases of malignant teratoma undifferentiated (MTU) and malignant teratoma trophoblastic (MTT) than malignant teratoma intermediate (MTI). Before therapy 14 patients had elevated serum markers, whilst in 5 patients markers were negative. Combination chemotherapy with Vinblastin, Bleomycin and Cisplatin (Einhorn) was given and afterwards 13 patients had to undergo operation to remove a residual mass. Scarring was found in 4 patients (31%), teratoma in 6 (46%) and active tumour in 3 (23%). At a median survival time of 3 years 16 of 19 patients (84%) are alive. The two patients with elevated tumour markers before operation are also alive and disease-free. Altogether out of 48 patients with advanced nonseminomatous testicular tumours 94% of the patients are alive.

[Sonographic follow-up of a 2-stage renal rupture]. / Sonographische Verlaufskontrolle bei zweizeitiger Nierenruptur.

The authors report on a two-stage rupture of the kidney that occurred in an eight-year old boy after a bicycle accident and was confirmed by sonographic diagnosis and by urography and surgery. Attention is drawn to the advantage and necessity of sonography, which is rapid, can be repeated any number of times, remains non invasive and is very accurate, as a diagnostic tool in renal trauma.

[Echographic differential diagnosis of scrotal contents. A contribution to evaluation of the method]. / Echographische Differentialdiagnostik des Skrotalinhaltes. Ein Beitrag zur Wertigkeit der Methode.

Ten patients were selected from a clinical material comprising 336 sonograms of the scrotal contents in order to discuss the differential diagnosis of testicular and extra-testicular conditions. The decision whether a tumour is testicular or extra-testicular does not usually pose a problem, but may be impossible for small peripheral tumours. The shape of the epididymis and vas deferens and the structure of the testes is of significance in the differentiation between torsion and epididymitis. Rare diseases--myxoliposarcoma, infiltrating urothelial carcinomas from the bladder growing along the vas, lymphangiomas--are considered in the differential diagnosis of space-occupying lesions. Lymphangiomas produce a typical appearance on ultrasound. The criteria for the diagnosis testicular trauma, rupture, parenchymal tears and haematocoeles are defined. Differentiating liquid from solid is rarely a problem. A testicular abscess in the presence of chronic orchitis can simulate a solid tumour.

Human chorionic gonadotropin-positive seminoma: is this a special type of seminoma with a poor prognosis?

Prognosis and treatment of HCG-positive seminomas with syncytiotrophoblastic giant cells are still a matter of discussion. Between 1977 and 1982 the serum HCG and alpha-feto protein levels were determined in a prospective study of a total of 51 patients presenting with histologically proven pure seminomas. A total of 13 of the 51 patients with pure seminoma had elevated serum HCG levels, but all of them were negative for alpha-feto protein. On clinical examination six patients had tumor Stage I, six had had tuor Stage II A-B and one patient had a tumor Stage III. The clinical stage was not found to correlate with HCG levels. In six patients presenting with tumors of clinical Stage II who underwent orchiectomy and subsequently radiation therapy there was a decrease in HCG levels following therapy. Five patients were followed for five years after therapy had been discontinued. There is no indication of a relapse in four patients, and the patients are negative or HCG. One patient suffering from a tumor, Stage IIB died three years later as a result of cirhosis of the liver. Autopsy did not reveal any signs of a residual tumor; the serum HCG levels were negative. For the time being HCG-positive seminomas should be classified and treated as a special morphologic form of seminoma.

Correlation of hormone levels and quantitative histological findings in testicular biopsies.

Testicular biopsies of 84 oligo- or azoospermic males with gonades of nearly normal size and without chromosomal abnormalities were studied by morphometric methods. The mean Johnsen score and the results of the morphometric investigations were plotted against the results of the hormone assays (plasma testosterone, LH, FSH, prolactin). High LH and FSH levels showed a very good correlation with the loss of germ cells, the tubular shrinkage and interstitial fibrosis. Plasma testosterone levels, however, did not correlate with any morphological structure of the testicular parenchyma. The Johnsen score and the morphometric findings can to some degree explain the relationship between morphological abnormalities and endocrinological findings.

[Epidermoid cyst of the testis]. / Epidermoidzyste des Hodens.

A very rare case of epidermoid cyst of the testis is being reported; the tumor was enucleated and the testicle preserved after evaluating the patient's history, clinical and especially ultrasonographic data. The literature is also being reviewed.

Morphology and incidence of testicular tumors in western Austria (1945-1980).

During the years 1945-1980 260 testicular tumors were registered in the two western provinces of Austria ( Tyrol and Vorarlberg ). The histological slices of these tumors were revised and classified according to the revised "British Classification" ( Pugh 1976). 91.9% of investigated testicular tumors were of germinal cell origin: 43.8% of them were seminomas and 38.1% teratomas. Combined tumors first appeared regularly when the surgical material was completely processed. The right side was more common affected than the left, in the ratio 7:5. The age of orchidectomy showed the typical peaks for seminomas, teratomas and combined tumors. 60% of germinal cell tumors were operated in stage pT3 (UICC). The average incidence of all testicular tumors in the years 1945-1980 was 1.9/100,000 males, but in the last decennium (1971-1980) the average incidence was 4.0, with a maximum of 6.9 in 1978. Districts with a high percentage of employed in agriculture and forestry showed lower incidences than industrialized areas.

[Injuries of the posterior urethra]. / Die Verletzung der hinteren Harnröhre.

Injuries of the posterior urethra are a result of a blunt trauma of the pelvic ring, lacerations of the perineum and iatrogenic perforations due to transurethral manipulations. Traumatic lesions of the posterior urethra in about 10% of these patients suffer also a bladder laceration. The diagnosis of a urethral injury is ascertained by i. v. urogram and urothrography. If a urethral trauma is suspected the insertion of a catheter should be avoided in any case. The treatment is divided in emergency treatment, which means evacuation and drainage of the haematoma and extravasation and suprapubic urinary derivation made by the surgeon and the primary realignment or delayed urethral reconstruction, both interventions being reserved for well trained urologists. Minimal lesions characterized by a preserved continuity in small extravasations in the urothrography are sufficiently treated by a suprapubic urinary diversion. Severe injuries are treated by realignment of the urethra over a splint, drainage of the perivesical space and urinary diversion. 63% of the patients treated by this modality had perfect results and there was no need for further therapy. The proper replacement of the fractured pelvic bones are an integrated part of our plan of treatment. About 12% of patients with pelvic fracture and injury of the posterior urethra experience loose their potency. These can be explained by neurovascular injury. Impotence does not seem to be caused by surgical treatment, since the rate of impotence is similar in patients treated by primary realignment and suprapubic urinary diversion only.

Exocrine and endocrine testicular function in patients with unilateral testicular disease.

Amongst 30 patients who had undergone untwisting and fixation for unilateral torsion of the testis, seminal analyses were normal in 15, equivocal in 3 and pathological in 12; and of 46 men with cryptorchidism who had had unilateral orchidopexy, seminal analyses were normal in 13, equivocal in 23 and pathological in 10. Follicle-stimulating hormone levels were found to be elevated in those with equivocal and pathological seminal analyses in both groups. Assessment of testicular function before orchidectomy in 36 patients with seminomas and non-seminomatous testicular tumours revealed only one (with a HCG-negative seminoma) with a normal seminal analysis. Men with HCG-positive testicular tumours were found to have decreased follicle-stimulating hormone levels and elevated 17-beta-oestradiol and prolactin levels.