Search

Several in vitro studies have addressed the interactions between estrogen/progesterone and human papillomavirus (HPV), but the results are controversial. We evaluated the effects of estrogen and progesterone and their antagonists on messenger RNA expression of HPV16 E6/E7 in HPV16-positive cell lines CaSki and SiHa with real-time reverse-transciptase polymerase chain reaction method. Colorimetric assay with tetrazolium salt (WST-1) and flow cytometry were used for testing proliferation and apoptosis. No statistically significant changes were found after hormone treatment in the expression of HPV16 E6/E7 or hormone receptors in CaSki and SiHa cell lines. Progesterone increased cell proliferation in both the cells, while estrogen increased proliferation of SiHa cells only. Estrogen seemed to protect the CaSki cells from apoptosis, and tamoxifen did not abrogate this effect. Progesterone slightly increased apoptosis of CaSki cells, and this effect was neutralized with RU486. In this study, estrogen and progesterone did not change either the transcription levels of HPV16 E6/E7 or estrogen receptor or progesterone receptor levels. Hormone receptor antagonists had no effect on transcription. Both hormones might have a permissive effect for the growth of cervical cancer, by promoting cell proliferation and making the cells vulnerable to mutations. In addition, estrogen acts as an antiapoptotic agent allowing growth advance of the cells infected with oncogenic HPV.

Although osteosclerotic metastases are characteristic of prostatic carcinoma, bone resorption is also accelerated. Since clodronate inhibits bone resorption and relieves bone pain, we have given it to patients with painful bone disease from prostatic cancer after failure of hormonal therapy. All patients received estramustine phosphate orally. Simultaneously they were randomly allocated to clodronate (36) and placebo (39) groups. Clodronate was given by mouth. The dose was 3.2 g for the first month, thereafter 1.6 g. Pain relief was more distinct in the clodronate group where one third of patients were totally free of bone pain. The use of analgesics stopped in 38% of patients on clodronate and in 18% on placebo which effect probably belongs to estramustine phosphate. Serum calcium concentration decreased more markedly in the clodronate group. Clodronate dose of 3.2 g seemed to be more potent than that of 1.6 g. Side effects were uncommon and occurred equally in both groups. No significant differences were seen in median survival or survival rates between the groups.

Department of Cardiothoracic Surgery, Helsinki University Hospital, FinlandKey words: Renal cell carcinoma; venous invasion; caval extension; surgery; prognosisin all cases (6). Immunohistochemical markers likeantifactor-VIII have proven to be useful in the searchof microscopic venous invasion (6, 7). Increasing thenumber of samples and slides per sample also im-proves the detection rate (6). Microvascular invasionhas turned out to be an independent prognosticfactor with adverse impact on disease-free survival(7, 8, 9). On the contrary and somewhat unexpected-ly, caval extension as such seems not to be an inde-pendent prognostic factor, if the tumour is comple-tely removed (4, 10, 11, 12). Hanke and coworkersexamined the surface structure of caval tumourthrombi with light- and scanning electrone micro-scopy and immunohistochemically by Q-band factorVIII marking (13). They found that the free floatingparts of the venous thrombi were covered with en-dothelium and compared this phenomen to abdomi-nal hernia covered with peritoneum.Thus microscopic venous invasion may result fromdifferent cellular mechanisms compared with mac-roscopic renal vein and caval extension.The speed of growth of the venous extension is notknown. Many patients with caval tumour thrombusand simultaneous metastatic disease will not under-go operation and die relatively quickly of the gener-alized tumour burden with no documentation of thegrowth speed of the venous part. The upwards prop-agation of the thrombus and its circumferential ex-pansion are most likely slow processes because inmany patients venous collaterals have time to be-come wide and there is no swelling of the lower ex-tremities. The tumour thrombus is for the most partloose from the caval wall but may invade the orifi-ces of the renal and hepatic veins, which has to betaken into account when planning the surgery (14).The terms extension and invasion should not bemixed. In cases of true invasion of the caval wall thisis also evident in microscopic examination (15). How-ever, wall invasion seems not to depend on the levelof the free thrombus (11).It is not clear how much blood circulation to thecells of the tumour thrombus comes from the renalarterial inflow, compared with possible diffusion

Orchiectomy and estrogens have been used for over 50 years in the treatment of advanced prostatic cancer. Although orchiectomy is a simple procedure, it may cause psychological stress. Oral estrogen therapy is as effective as orchiectomy in terms of cancer inhibitory effect, but its acceptance as primary hormonal treatment is overshadowed by an increased risk of cardiovascular complications. Parenteral estrogen, polyestradiol phosphate (PEP), is effective, but also associated with cardiovascular complications, although to a lesser extent. During the last 20 years, well tolerated luteinizing hormone releasing hormone (LHRH) analogues have been replacing orchiectomy and estrogens. Efforts have been made to increase the efficacy of the treatment by adding antiandrogens to LHRH analogues and also to orchiectomy (combined androgen blockade, CAB). However, the efficacy of LHRH analogues and CAB has not proved to be superior to that of simple orchiectomy and, moreover, they are expensive treatment modalities. Orchiectomy and LHRH analogues are associated with negative effects on bone mass and may cause osteoporosis, whereas PEP treatment has an opposite effect. Parenteral polyestradiol phosphate is still a cheap potential treatment for advanced prostatic cancer, but further studies should be conducted to establish its future role, e.g. combining acetylsalicylic acid to prevent cardiovascular complications.

Objective To determine whether immersion in antibiotic solution reduces or prevents bacterial adhesion onto biodegradable prostatic stents. Materials and methods Pre-cut segments of polyglycolic acid (PGA) and polylactic acid (PLA) prostatic stents were incubated with two common uropathogenic bacterial strains (Enterococcus faecalis and Escherichia coli) with and without previous immersion in antibiotic solution. Tobramycin, ceftriaxone and ciprofloxacin solutions were used, as these antibiotics are commonly administered for the prophylaxis and treatment of urinary tract infection (UTI). Results Immersion in ciprofloxacin solution prevented the adherence of both bacterial strains. Immersion in ceftriaxone solution prevented only the adherence of the E. coli strain. Immersion in tobramycin solution had no effect on either of the strains. The stent materials per se did not influence bacterial adhesion. After immersion in ciprofloxacin, the stent segments retained significant antibacterial activity even after one day's incubation in saline. Conclusion Immersion in a suitable antibiotic solution may significantly reduce and even prevent bacterial adhesion onto biodegradable prostatic stents. Preventing bacterial adhesion may reduce the risk of UTI during the use of these devices.

We tested the assumption that a positive pharmacological erection test implies normal penile vascular status.From March 1991 to February 1995, 372 patients with erectile dysfunction were referred to our institutions. Penile hemodynamics were studied in 205 patients with color coded Doppler ultrasonography after intracavernous injection of 40 micrograms. prostaglandin E1.Of the 205 patients undergoing color coded Doppler utrasonography 92 had a rigid erection, that is a positive pharmacological erection test. Doppler wave analysis showed that 76 of the 92 patients (82%) had normal and 7 (8%) had borderline arterial function (peak systolic velocity greater than 35 and 25 to 35 cm. per second, respectively), while 9 (10%) had arterial insufficiency (peak systolic velocity less than 25 cm. per second). All 92 patients had a normal veno-occlusive mechanism (resistance index greater than 0.90). Of the 9 patients with pure arteriogenic erectile dysfunction 8 had risk factors for arterial insufficiency, such as aortoiliac occlusive disease (5), diabetes mellitus (3), longer than 20-year smoking history (8) and hypertension (7).Our study shows hemodynamically that a positive pharmacological erection test does not rule out arteriogenic erectile dysfunction.

In an initial study of anti-nuclear antibodies in the chronic inflammatory bladder disease interstitial cystitis, we reported that 7% of interstitial cystitis patients studied had autoantibodies to the nucleolus. We now report that, using an autoimmune serum from a patient with interstitial cystitis, we have identified and partially characterized a novel protein with an M(r) of approximately 55 kDa (hereafter referred to as No55) localized to the granular component of the nucleolus. No55 was initially characterized by diffuse nucleolar immunofluorescence staining in interphase cells and by Western blotting as a 55-kDa doublet on whole-cell extracts. During mitosis, No55 was associated with chromosomes and appeared in prenucleolar bodies during telophase, but it did not colocalize with p80-coilin in coiled bodies. Immunoelectron microscopy revealed that No55 was localized uniformly throughout the granular component of the nucleolus compared with a more peripheral localization of nucleolar granular component protein B23. On segregation of the nucleolus with actinomycin D, No55 remained with the granular component of the segregated nucleolus, whereas protein B23 was found predominantly in the nucleoplasm. Finally, a cDNA expression library was screened with the human autoantibody against No55, and a 2.4-kb insert was isolated, subcloned to homogeneity, and then sequenced. Analysis of this sequence showed an open reading frame of approximately 1.3 kb coding for 437 amino acids with a predicted molecular weight of 50 kDa. A search of the gene sequence database indicated homology with SC65, a rat synaptonemal complex protein. Therefore, on the basis of molecular weight, nucleolar sublocalization, response to actinomycin D, and cDNA sequence determination, No55 is a novel protein of the interphase nucleolus.

Cyclosporine is a widely used immunosuppressive drug in organ transplantation and recently it has been used in several autoimmune disorders with good results. Because interstitial cystitis may have an autoimmune etiology, we wished to determine whether cyclosporine has any effect on symptoms in patients with severe interstitial cystitis.A total of 11 patients, who fulfilled the criteria for interstitial cystitis according to an international accrual form, received cyclosporine for 3 to 6 months at an initial dose of 2.5 to 5 mg./kg. daily and a maintenance dose of 1.5 to 3 mg./kg. daily. Blood pressure, serum creatinine and cyclosporine concentrations were monitored regularly. The patients completed frequency-volume charts at 2-week intervals.The frequency-volume charts showed favorable effects. Micturition frequency decreased (p0.01), and mean and maximum voided volumes increased significantly (p0.001 and p0.01, respectively). Bladder pain decreased or disappeared in 10 patients, allowing for storage of large urine volumes. Serum creatinine did not change with the dosages used. Mild hypertension occurred in 2 patients and resolved after the cyclosporine dose was lowered. After cessation of treatment symptoms recurred in the majority of patients.The findings revive the concept of interstitial cystitis as an autoimmune disease.

Our aim was to prove if alternating chemotherapeutic and immunotherapeutic instillations improved efficacy and reduced toxicity in patients with carcinoma in situ of the bladder.Of 68 carcinoma in situ patients randomly treated with instillations 40 received mitomycin C and 28 received mitomycin C and Pasteur bacillus Calmette-Guerin (BCG) in alternating courses. Mean followup was 33 months.The complete response rates with mitomycin C and mitomycin C/BCG were 45% and 71% at 3 months, 59% and 82% at 12 months, and 47% and 74% at 24 months, respectively (p = 0.041). The disease-free interval showed the superiority of alternating therapy (p = 0.043). Recurrence rates during the instillation period were 1.834 with mitomycin C and 0.922 with mitomycin C/BCG (p = 0.013). No remarkable side effects developed in the alternating group.Therapy of carcinoma in situ with alternating mitomycin C and BCG is more effective than mitomycin C alone. Compared to BCG monotherapy only few side effects occur.

In an infertility treatment programme for spinal-cord injured men, vibrator application was primarily used in cases of upper motor neurone lesion and electroejaculation in men with lower lesions, or when vibrator application failed to induce ejaculation. Spermatozoa were obtained by these methods from 29 out of 35 men who desired infertility treatment. No ejaculate was obtained from six men. Three of these men plus two others with very poor sperm quality with electroejaculation underwent micro-surgical sperm aspiration from the vas deferens for invitro fertilization (IVF), and spermatozoa were obtained from all of them. Thus it was possible to obtain spermatozoa from almost every spinal-cord injured man who had ongoing spermatogenesis using these three methods. Insemination was the primary infertility treatment used with all the couples where there was successful ejaculation. In all, 12 pregnancies resulted from home vaginal inseminations, eight from intrauterine inseminations, two from IVF with ejaculated spermatozoa, and two from IVF with spermatozoa aspirated from the vas. Three couples had children from donor inseminations (not counted in the results); 12 are still in the programme. From 24 pregnancies, 22 children have now been born to 18 couples out of the original 35 (51%), and there were four abortions. Hence, overall, infertility treatment of spinal-cord injured men has given good results.

The outcome of 137 ureteric injuries was analysed with respect to previous radiotherapy, site, type and length of the injury and time of treatment, to evaluate the prognostic significance of each of these factors. The length of the injury was the most important prognosticator of treatment outcome (P =0.0005). Previous radiotherapy and timing of treatment had prognostic significance (P =0.05) but the predictive value seemed to be linked to the frequent association with injury length. The site and the type of injury had no prognostic significance. The unfavourable prognostic significance of extensive injury length appeared to be related to the treatment procedures (urinary diversions) which in themselves carry a high failure rate. Knowledge of the impact of these factors on the outcome of ureteric injuries is valuable in choosing the best treatment option for each patient.

Although endoscopic optical urethrotomy is the primary treatment for urethral stricture, it is associated with a high recurrence rate, and the essential problem is how to stop the scar from shrinking after cutting. In a controlled study the effect of treatment of recurrent urethral stricture by internal urethrotomy followed by clean intermittent self-catheterization (CIC) for 6 or 12 months was compared in 25 and 24 patients, respectively. Patients learnt easily how to perform CIC: only one patient was not able to do it at home. All patients were evaluated by uroflowmetry before and immediately after urethrotomy, and 3, 6, 9 and 12 months later. Recurrence was defined as the need for further treatment. There was no difference in the recurrence rate between the two groups, but the maximum flow rate was significantly lower at 12 months in the patients who had ceased catheterization at six months. Complications included in two patients asymptomatic bacteriuria and in 10 patients symptomatic urinary infection. CIC is a very satisfactory method of managing patients with recurrent stricture, it is easy to learn, it prevents a decrease in the maximum flow rate and can thus be applied to most patients instead of regular bouginage. On the basis of the present study we could not determine any optimal time for the duration of CIC after urethrotomy, or whether it has any effect on the natural course of the disease.

The clinical efficacy, cardiovascular complications and mortality of polyestradiol phosphate (PEP) 160 mg/month i.m. were compared with the luteinizing hormone releasing hormone (LHRH) analog, buserelin, in a prospective, randomised multicentre study including 147 patients with prostatic cancer. The cumulative non-progression rate at three years was 0.53 in the PEP group and 0.70 in the LHRH group. The mortality from cardiovascular diseases was the same in the two treatment groups. The parenterally given PEP was not associated with an increased risk of cardiovascular complications. The dosage of PEP 160 mg monthly seems, however, to be insufficient in the treatment of prostatic cancer.

The outcome of 24 patients affected by bilateral injuries of the ureter after gynaecological and obstetric procedures was analyzed. Five patients were not treated because they were asymptomatic, while 19 patients underwent different kinds of surgical procedures. Ureteric stenting was performed in 4 patients, reconstructive procedures in 9, internal diversions in 2 and external diversions in 4. Good results were achieved in 14 (74%) of the 19 treated patients. The success rate, however, was remarkably higher (85%) in the group of patients treated with ureteric stenting or reconstructive procedures than in those treated with diversions (50%). Ureteric stenting and bilateral reconstructive procedures, when feasible, constitute the simplest and safest way to repair short ureteric injuries. In the management of extensive injuries nephrostomy represents a safe and valid alternative to open surgical diversions which do not improve the quality of life and may even be life-threatening.

The cytotoxicity of latex urinary catheters has been earlier documented. During the manufacturing process tens of chemicals are added to the natural rubber base. Several of the accelerators and other chemicals used have carcinogenic and acute toxic effects. Some of the accelerators are zinc compounds. In the present study, the cytotoxicity and zinc concentration of 68 latex catheter extracts were analysed. The siliconized latex catheters were the most toxic, and a correlation was seen between the IC50 values and the zinc concentration. The good manufacturing practice (GMP) has to some extent resolved the cytotoxicity problem of latex urinary catheters. There is, however, still a need to reformulate the manufacturing process and to find new catheter materials to meet the new EN standards concerning the biological safety of urinary catheters.

Adrenal myelolipoma is an uncommon benign tumor usually discovered by chance in patients with hypertension, obesity, arteriosclerosis or cancer. The association with adrenocortical endocrine dysfunctions is rare. We report herein an unusual case, the second in the literature to the best of our knowledge, of combined adrenal adenoma and myelolipoma in a patient with Conn syndrome.

A müllerian adenosarcomalike tumor of the seminal vesicle is described in a 49-year-old man. The tumor occupied the entire right seminal vesicle and adhered to the right lobe of the prostate, in the area adjacent to the seminal vesicle. The tumor was also adherent to the rectum. Microscopically, the cells were seen to invade the prostatic tissue. The tumor consisted of a highly cellular stroma with spindle-shaped pleomorphic cells, suggesting the diagnosis of a low-grade sarcoma. In addition, dilated cystic spaces lined by columnar epithelium were seen. Immunohistochemically, most tumor cells showed positivity for vimentin, desmin, and muscle-specific actin, suggesting smooth-muscle cell differentiation. Furthermore, electron microscopy also demonstrated smooth-muscle differentiation of the tumor cells. The patient has been disease-free for 48 months since undergoing a cystoprostatetectomy.

There is still much controversy about the diagnostics and therapy of carcinoma in situ (TIS/CIS) of the bladder. Reliance on cytological possibilities in the primary diagnosis and grading varies in separate centres. Hence, the small series published hitherto are often incomparable due to different start points and end points of trials. We regard cytology as the key examination in TIS. Complete response (CR) and progressive disease (PD) are end points which can be defined by histology/cytology and the timer factor. Our philosophy concerning the evaluation of therapy-principles in superficial bladder cancer is mainly based on our own experience. The efficacy of MMC and of BCG was equally modest in the Finnbladder I study: the CRs 38% and 40%; the PDs 8% and 20%, respectively. The interim of the ongoing Finnbladder II study are more promising after 6 months follow-up: the CR with MMC 67% and with alternating therapy with MMC and BCG 80%; there were no progressions so far. The primary grade of TIS has been a significant prognostic factor for instillation therapy in our earlier series of 62 pts since 1976. There were no progressions of grade I but 19% of grade II and 13% of grade III. A wide consensus of concepts dominates as to the superficial bladder cancer (Ta-T1). The recurrence rate (RR) and the recurrence index (RI/m) as the end points of prophylactic trials are capable of indicating the recurrence-preventive efficacy of different instillations, allow the use of a patient as his own control, and are suitable for statistical evaluation (table I).(ABSTRACT TRUNCATED AT 250 WORDS)

In an infertility treatment programme for spinal-cord injured men, vibrator application was primarily used in cases of upper motor neurone lesion and electroejaculation in men with lower lesions, or when vibrator application failed to induce ejaculation. Spermatozoa were obtained by these methods from 29 out of 35 men who desired infertility treatment. No ejaculate was obtained from six men. Three of these men plus two others with very poor sperm quality with electroejaculation underwent micro-surgical sperm aspiration from the vas deferens for invitro fertilization (IVF), and spermatozoa were obtained from all of them. Thus it was possible to obtain spermatozoa from almost every spinal-cord injured man who had ongoing spermatogenesis using these three methods. Insemination was the primary infertility treatment used with all the couples where there was successful ejaculation. In all, 12 pregnancies resulted from home vaginal inseminations, eight from intrauterine inseminations, two from IVF with ejaculated spermatozoa, and two from IVF with spermatozoa aspirated from the vas. Three couples had children from donor inseminations (not counted in the results); 12 are still in the programme. From 24 pregnancies, 22 children have now been born to 18 couples out of the original 35 (51%), and there were four abortions. Hence, overall, infertility treatment of spinal-cord injured men has given good results.

In a review of 127 urethrocystograms carried out on 92 males with spinal cord injury the following conclusions were drawn. (1) In the presence of vesico-ureteric reflux or urethral reflux into the male adnexa, bladder outlet obstruction should be suspected. (2) Lesions of the anterior urethra develop easily as the result of indwelling catheterisation in patients lacking sensation. A retrograde urethrogram is necessary to demonstrate these lesions. (3) Severe trabeculation of the bladder wall can be a sign of high-pressure outlet obstruction. (4) Dilatation of the bladder neck in patients with detrusor sphincter dyssynergia may lead to total urinary incontinence after sphincterotomy. (5) Urethrocystography is not a valid investigation to detect bladder stones.

Urological evaluation was performed on 63 spinal cord injury patients with micturition difficulties or repeated urinary tract infections. Detrusor external sphincter dyssynergia of varying degree was found in 36/63 (57%) of these patients with urological problems, and 15/36 (42%) of them were estimated to benefit by external sphincterotomy. Sphincterotomy was carried out in 11 patients. The effect on micturition problems was good, but intermittent bacteriuria continued despite the operation. However, marked febrile urinary tract infections appeared to subside.

Two hundred and six intravenous urograms on 119 patients with spinal cord injury were reviewed and the findings correlated with the clinical data. Fifty (42%) of 119 patients had pathological changes in their upper urinary tracts. The most common feature was impaired renal emptying. Patients with normal and pathological upper tracts had similar findings according to the number of positive urine cultures during the first post-injury year, but in the follow-up those with pathological urograms showed bacteriuria significantly more often. Febrile urinary tract infections at least once a year were encountered in the follow-up of 40% of the patients with pathological urograms, as compared with 8% with normal urograms. All patients with severe renal changes had impaired emptying from the kidneys. This supports the view that the basic patho-physiological mechanism leading to upper tract deterioration in patients with spinal cord injury is a functional or mechanical obstruction of the lower urinary tract. This should be treated actively before irreversible renal changes develop.

The cystometrographic patterns together with anal sphincter electromyograms of 62 patients with recent spinal cord injury were analysed. Four main patterns could be distinguished. The patients with well-developed detrusor reflex gained easy emptying of the bladder significantly more often than those with supranuclear injury but weak or unsustained detrusor contractions, or those with mixed spinal lesions. The patients with mixed lesions and low compliance bladders had the most severe incontinence problems. One fourth of the total series had various degrees of upper tract dilatation in their first urogram, and these changes occurred more often in patients with high detrusor activity. Urinary tract infections occurred in all patients but less often in those with areflexic bladders. This group of patients was also most suitable for intermittent self-catheterisation.

The characteristics of urinary tract complications in a series of 202 spinal cord injury patients are described. Repeated urinary infection was the most usual problem. Upper urinary tract changes were detected in 61 patients (30%). 56 patients (28%) underwent bladder outlet surgery for problems with voiding. Urinary diversion was done to 8 patients (4%), and 12 (6%) were treated with permanent indwelling catheter or self-catheterization. The high incidence of bladder stones (29%) and urethral complications (14%) was regarded as due to indwelling catheterization at the early stage post-injury. Despite the high urinary tract morbidity, only one patient has so far died of renal failure.

Four hundred and four prostatic cancer patients diagnosed in the years 1979-1982 in nine Finnish hospitals have been followed up for a mean period of three years. The aim of this study is to evaluate the situation of this malignancy in the Finnish male population and to discuss the diagnostic procedures and treatment modalities. In one fifth of the patients the carcinoma was as incidental finding on microscopical examination of tissue removed by transurethral resection or enucleation for presumed benign prostatic hyperplasia. At the diagnostic moment 69% of the tumours were locally advanced beyond the prostatic capsule and one third of all cases had metastasized. 134 out of 404 (33%) have died and 45% of these of prostatic cancer. Survival was adversely affected by the tumour differentiation grade. In non-metastasized cases the local extent of the tumour had no notable effect on prognosis. Some early comparisons are made between orchidectomy and oestrogen therapy.

Monitoring of the urinary output is mandatory during open-heart surgery and in the immediate postoperative period. During 1980-81 we noticed an alarming rise in the number of post-catheterization urethral strictures affecting men who had undergone open-heart surgery. To avoid this serious complication, we switched from conventional urethral catheterization to suprapubic cystostomy for these patients. The first 93 cases with suprapubic drainage have now been analysed as regards the advantages and complications of this technique. The advantages were clear: The patients were satisfied with the method and no urethral strictures developed. The only side effect was haematuria, which in 9 cases led to occlusion of the catheter and required extraneous maneouvres. Suprapubic cystostomy thus seems to be a good alternative to conventional urethral catheterization in open-heart surgery. The possible causes of the urethral complications in this particular group of patients also are discussed.