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Biomedical subjects

S Hellsten

Publications and source records attributed to S Hellsten.

At least 19 recordsLinked to original sources

Ammonia emission and deposition in Scotland and its potential environmental impacts.

The main source of atmospheric ammonia (NH3) in Scotland is livestock agriculture, which accounts for 85% of emissions. The local magnitude of emissions therefore depends on livestock density, type, and management, with major differences occurring in various parts of Scotland. Local differences in agricultural activities therefore result in a wide range of NH3 emissions, ranging from less than 0.2 kg N ha(-1) year(-1) in remote areas of the Scottish Highlands to over 100 kg N ha(-1) year-1 in areas with intensive poultry farming. Scotland can be divided loosely into upland and lowland areas, with NH3 emission being less than and more than 5 kg N ha(-1) year(-1), respectively. Many semi-natural ecosystems in Scotland are vulnerable to nitrogen deposition, including bogs, moorlands, and the woodland ground flora. Because NH3 emissions occur in the rural environment, the local deposition to sensitive ecosystems may be large, making it essential to assess the spatial distribution of NH3 emissions and deposition. A spatial model is applied here to map NH3 emissions and these estimates are applied in atmospheric dispersion and deposition models to estimate atmospheric concentrations of NH3 and NH4+, dry deposition of NH3, and wet deposition of NHx. Although there is a high level of local variability, modelled NH3 concentrations show good agreement with the National Ammonia Monitoring Network, while wet deposition is largest at high altitude sites in the south and west of Scotland. Comparison of the modelled NHx deposition fields with estimated thresholds for environmental effects ("critical loads") shows that thresholds are exceeded across most of lowland Scotland and the Southern Uplands. Only in the cleanest parts of the north and west is nitrogen deposition not a cause for concern. Given that the most intense effects occur within a few kilometres of sources, it is suggested that local spatial abatement policies would be a useful complement to traditional policies that mitigate environmental effects based on emission reduction technologies.

Ammonia↗

Guidelines on renal cell cancer.

OBJECTIVES: On behalf of the European Association of Urology (EAU), Guidelines for Diagnosis, Therapy and Follow-Up of Renal Cell Carcinoma Patients were established. Criteria for recommendations were evidence based and included aspects of cost-effectiveness and clinical feasibility. METHOD: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts on renal cell carcinoma (RCC). RESULTS: RCC is characterised by a constant rise in incidence over the last 50 years, with a predominance of men over women and an incidence peak in the 6th and 7th decade. There is no risk factor established and the current TNM system (UICC, 1997) is endorsed for staging purposes. Clinical signs and symptoms of RCC are becoming less frequent, incidental discovery constitutes already a majority of cases. Diagnosis is established by ultrasound and abdominal CT, extension assessment in routine cases is done by chest X-ray. Additional examinations may be required in select cases. The therapy of choice in organ-confined RCC is surgery. Radical tumour nephrectomy is considered as a standard. Efficacy and side-effects of organ-sparing surgery, lymphadenectomy and inclusion/omission of ipsilateral adrenalectomy in selected cases is a matter of ongoing clinical research. In metastatic cases, tumour nephrectomy should only be considered in the context of modern systemic immunotherapy. A follow-up at regular intervals is recommended because certain cases of recurrences may be candidates for surgery and/or immunomodulating therapy. CONCLUSION: A rise in incidence, improved diagnostic procedures, and evolving multimodality therapeutic concepts justify the need for rational guidelines on this most challenging urologic malignancy.

Carcinoma, Renal Cell↗

The Nordic experience of cooperative urinary bladder cancer trials.

The Nordic Urological Association Urothelial Group has been organizing phase 3 trials in urinary bladder cancer therapy since 1986. In total, around 1,000 patients from three countries have entered these studies. The results of the different trials are reviewed, and the problems with cooperative trials are discussed. The importance of these kind of trials in setting up management guidelines is underscored.

Finland↗

The effect of isoniazid on BCG-induced toxicity in patients with superficial bladder cancer.

The use of bacillus Calmette-Guérin in the treatment of transitional cell cancer of the bladder has caused concern because of its associated adverse effects. We conducted a randomized prospective, double-blind, multicentre study to determine whether isoniazid prophylaxis could reduce BCG-induced toxicity without compromising its immunotherapeutic effects. Patients (n = 160) with histologically documented urothelial cancer (pTa-T1, pTis, G1-3) were treated with 6 weekly instillations of BCG Connaught strain, 81 mg, administered concomitantly with a 3-day course of isoniazid (300 mg o.d.) or placebo. Side-effects were recorded with each treatment and at follow-up. Of the patients treated with isoniazid, 19% remained free from side-effects, compared with 16% of the placebo group. Local side-effects confined to the bladder were significantly lower among those receiving isoniazid (35% vs. 48%, p < 0.01). Local side-effects together with systemic adverse effects such as fever, nausea or skin rash were experienced by 30% of patients in each arm. There were no differences in tumour recurrence between the two patient groups. Concomitant isoniazid reduces the local, but not the systemic side-effects of topically applied BCG without compromising the antitumour effect on superficial, transitional cell cancer of the bladder during a follow-up period that now exceeds 2 years.

Administration, Intravesical↗

Precancerous lesions in the kidney.

Renal cell carcinoma (RCC), although occurring less frequently than prostate and bladder cancer, is actually the most malignant urologic disease, killing >35% of affected patients. Therefore, investigation of the nature of premalignant lesions of the kidney is a relevant issue. Following the most recent histological classification RCC can be subdivided into four categories: conventional RCC; papillary RCC; chromophobe RCC; and collecting duct carcinoma. In contrast to many genitourinary malignancies, premalignant alterations in the kidney are scarcely described. Intratubular epithelial dysplasia has been recognized as the most common precursor of RCC. In analogy to prostatic intraepithelial neoplasia (PIN), the premalignant lesions of the kidney are described as high or low-grade renal intratubular neoplasia. In contrast, precancerous lesions have been described as part of the von Hippel-Lindau syndrome (VHL) where the evolution from a simple cyst to an atypical cyst with epithelial hyperplasia to cystic or solid conventional-type RCC is well documented. Finally, in the genesis of papillary RCC an adenoma-carcinoma sequence has been recognized with specific genetic changes. There are no data on the epidemiology of premalignant lesions of the kidney, but research into the etiology of RCC has been extended substantially. Familial and genetic factors are well documented in VHL disease, in hereditary papillary RCC, in the tuberous sclerosis complex and in familial RCC. Cigarette smoking and obesity are established risk factors for RCC. Hypertension or its medication has also been associated with an increased risk. Among dietary factors an inverse relation between risk and consumption of vegetables and fruit has been found. Occupational exposure to substances such as asbestos and solvents has been linked to an increased risk of RCC. Specific RCC variants have distinctive chromosome alterations and several genes have been implicated in the development of RCC. Loss of material from the 3p chromosome characterizes conventional RCC and the deletion of the VHL suppressor gene plays an important role in the genesis of this RCC variant. In contrast, numerical changes with trisomy of chromosomes 7 and 17 and loss of the sex chromosome are typical changes in papillary tumors, whereas papillary RCC have additional trisomies. Chromophobe RCC is characterized by loss of chromosomes with a combination of monosomies. Less consistent genetic alterations are associated with collecting duct carcinoma. The traditional treatment of RCC is surgery by radical or partial nephrectomy. The latter approach carries a risk of tumor recurrence as a result of unrecognized satellite lesions or premalignant lesions that might have been present at the time of surgery. However, the reported recurrence rates after partial nephrectomy are <1% and therefore the possible presence of premalignant disease does not alter the actual treatment strategy advocated. Although multifocality and bilateral occurrence of RCC are much more likely in cases of papillary RCC, biopsy of the renal remnant or contralateral kidney is not justified even in patients with this tumor type. Conversely, patients with RIN in a partial or radical nephrectomy specimen or in a renal biopsy taken for whatever reason should be subjected to closer follow-up with regularly repeated ultrasound. When an effective chemopreventive regimen becomes available it might be useful for patients with an inherited risk of RCC as well as in those who are at risk of tumor recurrence after intervention. Mass screening with the purpose of detecting RCC at its earliest stage is not recommended at the present time, but screening focused on certain risk groups can be advocated. Further research is needed to identify avoidable risks, develop effective chemoprevention and recognize patients at risk.

Carcinoma, Renal Cell↗

Lymphatogenous spread of renal cell carcinoma: an autopsy study.

PURPOSE: We investigated the occurrence and extent of metastatic spread, especially regarding lymph nodes, of renal cell carcinoma. MATERIALS AND METHODS: From 1958 to 1982, 554 cases of renal cell carcinoma were diagnosed at autopsy. Clinical data and autopsy findings were reevaluated, and the occurrence of lymph node metastases was analyzed by histological examination of retroperitoneal, mediastinal, supraclavicular, axillary and inguinal lymph nodes. RESULTS: Distant metastases were revealed in 119 cases (21.5%), including 31 (5.6%) with single metastases. In 88 cases (16%) renal cancer was the cause of death. Lymphatogenous dissemination was detected in 80 cases of which 75 had additional, mostly multifocal metastatic spread. Consequently lymph node metastases restricted to the paracaval and/or para-aortic lymph nodes were noted in only 5 cases (0.9%). CONCLUSIONS: Of the 554 cases of clinically unrecognized renal cell carcinoma almost all with lymphatic spread had additional distant metastases. Therefore, the therapeutic effect of extensive retroperitoneal lymph node dissection in association with radical nephrectomy seems to be low. However, more limited lymph node dissection may be useful, mainly as a staging procedure.

Adult↗

Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial I. The Nordic Cooperative Bladder Cancer Study Group.

PURPOSE: Chemotherapy is widely used in patients with locally advanced bladder cancer but until now there has been no conclusive evidence that this therapy improves survival. The Nordic Cooperative Bladder Cancer Study Group conducted a randomized phase III study to assess the possible benefit of neoadjuvant chemotherapy in patients with bladder cancer undergoing radical cystectomy after short-term radiotherapy. MATERIALS AND METHODS: Our trial included 325 patients with locally advanced stage T1 grade 3 or stages T2 to T4aNXM0 bladder cancer allocated randomly into a chemotherapy or no chemotherapy group (control). The chemotherapy schedule consisted of 2 cycles of 70 mg./m.2 cisplatin and 30 mg./m.2 doxorubicin with a 3-week interval between the cycles. RESULTS: After 5 years the overall survival rate was 59% in the chemotherapy group and 51% in the control group (p = 0.1). The corresponding cancer specific survival rate was 64 and 54%, respectively. In regard to treatment, no difference was observed for stages T1 and T2 disease, while there was a 15% difference in overall survival for patients with stages T3 to T4a disease (p = 0.03). In a multivariate analysis only chemotherapy and T category emerged as independent prognostic factors. The relative death risk for patients who received chemotherapy was 0.69 (95% confidence interval 0.49 to 0.98) compared to the control group after adjustment for the other tested factors. CONCLUSIONS: Neoadjuvant chemotherapy seems to improve long-term survival after cystectomy in patients with stages T3 to T4a bladder carcinoma, while no survival benefit was found for stages T1 to T2 disease.

Antineoplastic Combined Chemotherapy Protocols↗

Determination of the relative glomerular filtration rate of each kidney in man. Comparison between iohexol CT and 99mTc-DTPA scintigraphy.

Iohexol and 99mTc-DTPA were used in 43 patients to determine the relative glomerular filtration rate (GFR), i.e., the GFR of each kidney in percent of total GFR. The amount of any GFR marker accumulating in Bowman's space, tubuli and renal pelvis within a few minutes after i.v. injection, before any marker had left the kidney via the ureter, was defined as proportional to the GFR of that kidney. The renal accumulation of iohexol was determined by CT using 10 slices of 8-mm thickness 1 to 4 minutes after injection. The renal accumulation of 99mTc-DTPA was determined with a gamma camera within 2 minutes after injection. The correlation coefficient between the two methods was 0.98. Due to the higher radiation dose from CT than from 99mTc-DTPA injection, relative GFR determination with CT should be performed when there is also a diagnostic need to reveal morphology.

Adolescent↗

Laser treatment of localized squamous cell carcinoma of the penis.

PURPOSE: We evaluate the efficacy and morbidity of laser and conventional treatment in 32 men with penile cancer. MATERIALS AND METHODS: Of 32 men treated for squamous cell carcinoma of the penis observed for an average of 44 months 19 were treated with the combined carbon dioxide and neodymium: YAG lasers. The 13 patients treated conventionally had more advanced disease and they were a mean 17 years older than those in the laser treated group. RESULTS: All laser treated patients were disease-free after a mean of 31 months. Among the 13 conventionally treated patients there were only 5 long-term survivors. CONCLUSIONS: The cosmetic and functional outcome of laser treatment for stages Tis to T2N0M0, grades 1 and 2 squamous cell carcinoma of the penis is excellent, and the associated morbidity rate is low.

Adult↗

Uptake and distribution of intravenously or intravesically administered photosensitizers in the rat.

Photodynamic therapy using i.v. injected porphyrin photosensitizers have been used to treat selected cases of superficial bladder cancer. Since cutaneous photosensitivity, lasting 6-8 weeks, is a well known undesirable side effect of this therapy, we instilled the photosensitizers intravesically in rats and compared the uptake of photosensitizers in different tissues by this route of administration with the uptake after intravenous injection. The intravesical mode of delivery enhanced photosensitizer uptake in the bladder wall, while giving low concentrations in extravesical organs. Intravesical instillation of the photosensitizers may therefore increase their efficacy and reduce phototoxicity as compared with intravenous injection. Comparing the results obtained by two assays, one based on porphyrin fluorescence and the other based on the application of radioactively labelled photosensitizers, it was concluded that the i.v. administration route may result in tissue uptake of significant amounts of aggregated non-fluorescent, supposedly inactive drug, while the intravesical administration led to less uptake of aggregates relative to active drug monomers.

Animals↗

Carbon dioxide laser treatment of lichen sclerosus et atrophicus.

We followed 62 men treated with the carbon dioxide laser for lichen sclerosus et atrophicus for an average of 30 months (3 months to 7 years). Of the patients 47 (76%) became asymptomatic and 10 (16%) had minor residual symptoms. In 26 patients (40%) concomitant superficial meatal stenosis was simultaneously treated with laser meatotomy. The cosmetic and functional results of treatment were highly encouraging. Provided that radicality is achieved at the primary application, the carbon dioxide laser is an excellent therapeutic modality for lichen sclerosus et atrophicus.

Adult↗

Neoadjuvant chemotherapy in bladder cancer: a randomized study. Nordic Cystectomy Trial I.

An analysis by the Nordic Cooperative Bladder Cancer Study Group concerned the possible benefit of neoadjuvant chemotherapy--given before scheduled low-dose irradiation and cystectomy. In the trial, started in 1985, 311 patients with locally advanced bladder cancer, T1 grade 3, T2-T4a NXMO, were randomly allocated to a 'chemotherapy' or a 'no chemotherapy' group. Chemotherapy consisted of two cycles comprising cisplatin 70 mg/m2 and doxorubicin 30 mg/m2, with a 3-week interval between cycles 1 and 2. All patients were locally irradiated with 4 Gy daily for 5 consecutive days. The follow-up included 266 cystectomized patients. In May 1992 the mean observation time was 18 months for all patients and 47 months for those still alive. The results suggest that a significant downstaging in the group randomized to chemotherapy was found only in T1, grade 3 tumours (56 patients, p = 0.002). The overall survival rate in all 311 patients was significantly higher in the chemotherapy group (p = 0.03) and likewise among the 253 patients with T2-T4a tumour (p = 0.018). For the 210 patients who underwent cystectomy for T2-T4a tumour, there was a trend towards longer survival when chemotherapy was given (p = 0.057). Patients with initially muscle-invasive tumour who responded to neoadjuvant treatment survived longer than non responders (p = 0.0005). The results suggest that neoadjuvant chemotherapy improve the outcome of radical surgery for muscle-invasive bladder cancer, though the effect on long-term survival is inconclusive. Further studies on the effect of neoadjuvant chemotherapy is initiated.

Antineoplastic Combined Chemotherapy Protocols↗

Compartment syndrome after prolonged surgery with leg supports.

Compartment syndrome has been reported in a few cases after prolonged surgery with patients in leg supports. A recent case in our hospital (57-year-old man undergoing cystourethrectomy because of cancer) made us interested in the problem. This case together with six from the literature are analysed. Moreover, the first 11 cases operated on with a pelvic pouch and ileoanal anastomosis at our department were reviewed. They had been in the leg support position for a median duration of 6.4 (5.8-8) h. In four of them leg pain and swelling developed within 12 h. Three showed regression within a few days, one after a week. In one patient with swelling compartment pressure was measured with a transducer tipped catheter. Intermittently the pressure was up to 50 mm Hg. There was an obvious decrease in pressure on knee bending. Also, in a patient without swelling large pressure variations were seen but not to critical levels.

Adult↗

Intravesical mitomycin C for carcinoma in situ of the urinary bladder.

Mitomycin C was given intravesically over periods of 2-32 months to 34 patients with carcinoma in situ of the urinary bladder. Initial complete response was obtained in 17 patients, 14 of whom remained without evidence of disease during follow-up averaging 28 months from cessation of mitomycin therapy. In three responding patients malignant cells reappeared in the urine during follow-up, although no recurrence of carcinoma could be proven in bladder biopsy specimens. In eight of the 17 non-responders, muscle invasion and/or metastatic disease developed during or after mitomycin treatment. The prostatic urethra was involved in five cases. Chemotherapy had to be discontinued because of chemical cystitis in three cases. Mitomycin C appears to be effective for intravesical treatment of carcinoma in situ of the urinary bladder. Close surveillance of these patients is mandatory, however, and must include monitoring not only of the bladder, but also of the prostatic urethra and the upper urinary tract.

Administration, Intravesical↗

Current status of epirubicin (Farmorubicin) in the treatment of solid tumours.

Epirubicin (Farmorubicin) is a drug of significant interest in the treatment of a variety of solid tumours and a comprehensive review of reported investigations is given. From experimental and clinical studies it appears that in general doxorubicin and epirubicin exhibit no qualitative, but only some quantitative, differences. Thus, the pharmacokinetic and pharmacodynamic characteristics of the two drugs are essentially similar, as are the tumour spectrum and the level of their clinical efficacies. To achieve haematological equitoxicity of the two drugs the dose of epirubicin should be approximately 20% higher than that of doxorubicin, giving rise to a higher cumulative dose of epirubicin. On the other hand, epirubicin is significantly less cardiotoxic than doxorubicin. Thus, the recommended cumulative dose of doxorubicin is 500 mg/m2 and the corresponding figure for epirubicin is 1,000 mg/m2. For either drug a number of questions are still left open, the most important of which include the questions about optimal treatment schedules and the existence of a clinical relevant dose/efficacy relationship.

Antineoplastic Combined Chemotherapy Protocols↗