Tumour thrombus consistency has no impact on survival in patients with renal cell carcinoma.

The prognosis of renal cell carcinoma (RCC) with venous tumour thrombus (VTT) is variable and not always possible to predict. The prognostic impact and independence of tumour thrombus-related factors including the recently introduced tumour thrombus consistency (TTC) on overall survival remain controversial. The aim of this study was to investigate the prognostic role of TTC in patients' survival. We determined the tumour thrombus consistency (solid vs. friable) in a cohort of 84 patients with RCC and VTT who underwent nephrectomy with thrombectomy, and performed a retrospective evaluation of the patients' data from the prospectively maintained database. A total of 45% of patients had solid thrombus (sTT) and 55% had friable thrombus (fTT). The venous tumour thrombus consistency was not predictive of overall survival. Further studies, preferably prospective and with a larger number of patients, are needed to validate the obtained results, as well as to evaluate the usefulness of tumour thrombus consistency in clinical practice for stratifying the risk of recurrence and planning further follow-up.

The future of chronic diseases.

Major chronic diseases continue to be the main health scourge of the most developed countries, have only recently been retreating in frequency in the fledgling market economies, and are becoming dominant in many populous areas of the developing world. The descriptive evidence from the developments of the near past strongly suggests that much of the control outcomes have already been achieved with the existent imperfect causative knowledge. The continuation of desirable trends in major chronic diseases in some places like Central & Eastern Europe, is uncertain within the intermediate time range without gaining more etiological clues, among which the role of medical care is worthy of reconsideration. Other factors can grow in importance, like obesity, which may be freed from the suppressive influence of cigarette smoking to trigger major mass pathologies, like type 2 diabetes mellitus, arterial hypertension, some cancers etc. The role of social underpriviledge seems recalcitrant, although the part played by social share of biological risk agents may diminish in response to educational persuasion. The remotest destinies of some chronic diseases may depend on the mixture of external and genetic influences ending as predispositions towards some ailments, antecedents of which might have protected their carriers from dangers of the past unfriendly environment, like obesity (or diabetes) against famine, or hypertension against inefficient defense reaction. The resulting medium-range prediction of well-being for inhabitants of more developed world may not be forbidding, since increasing life expectancy needs not be synonymous with disability, and attaining old age does not require excessive sacrifice, beyond reducing number smoked, or preserving decent respiratory volumes.

Using model-system genetics for drug-based target discovery.

The combination of medicinal chemistry and model-organism genetics is emerging as a powerful tool for the discovery and validation of drug targets. Model systems can be used to identify the cognate target for compounds that demonstrate in vivo efficacy but have unknown mechanisms of action. Alternatively, drugs with known cognate targets can be used to probe biochemical pathways in model organisms, revealing new targets and mechanisms within these pathways. In both cases, the availability of human genomic sequence data is opening up new opportunities for accelerating target discovery.

[Clinical and immunohistoenzymatic investigations in patients with vasomotor and perennial allergic rhinitis]. / Badania kliniczne i immunohistoenzymatyczne u chorych z naczynioruchowym i calorocznym alergicznym niezytem nosa.

The aim of our study was evaluation of the results of clinical examination in patients with vasomotor and perennial allergic rhinitis and assessment of number of blood vessels, nerve fibres and mast cells on the basis of immunohistoenzymatic examination. There were 42 patients examined aged from 18 to 50 and divided into three groups: I--16 patients with vasomotor rhinitis and II--14 patients with perennial allergic rhinitis and III--12 patients (control) with nasal septum deviation. On the basis of the patient's history data, clinical otorhinolaryngologic examination and active anterior rhinomanometry the patients were qualified to bilateral inferior turbinectomy. The nasal mucosa removed during surgery underwent immunohistoenzymatic examination using the monoclonal antibody against the tryptase of mast cells (MCT company, DAKO), the endothelin of blood vessels (EC - DAKO) and the neurospecific enolase (NSE - DAKO). In examined groups of patients with vasomotor and perennial allergic rhinitis and control group similar escalation of clinical symptoms expressed by means of points index were stated. In immunohistoenzymatic studies the differences in mean number of blood vessels and nerve fibres between examined groups were not statistically significant, however statistically significant difference concerned higher number of mast cells patients with vasomotor rhinitis in comparison to perennial allergic rhinitis.

[Stereotactic biopsy and brachytherapy in the diagnostics and treatment of brain tumors--preliminary report]. / Wczesne wyniki zastosowania biopsji stereotaktycznej i brachyterapii w diagnostyce i leczeniu guzów mózgu.

Promising results have been obtained using brachytherapy in the treatment of brain tumors. Between November 99 and August 2000, 28 patients with brain tumors (15 newly diagnosed gliomas, 11 recurrent gliomas, 2 metastases) underwent implantation of temporary iridium 192 sources with stereotactic technique. This group received external beam radiation therapy (45 Gy) following implantation. Patients were followed-up with CT scans every 3 months. Serious complications occurred in two patients (postradiation brain oedema). Median survival has not been assessed due to short follow-up period and small number of patients. Further clinical assessment is required especially long-term follow-up. Brachytherapy appears to be a useful technique for the treatment of selected brain tumors.

[Mortality from cardiovascular diseases in patients with type 2 diabetes]. / Umieralnosc z powodu chorób ukladu krazenia u chorych na cukrzyce typu 2.

In the period 1973/74-1995 a prospective observation was carried out on 4420 diabetic patients (1990 males and 2430 females) aged 30-68 years, with type 2 (non-insulin dependent diabetes) of 1-10 years duration. During the 22-year period nearly 80% of the initial cohort died. The risk of death was 2-times higher in diabetes than in the samples of general population observed at the same time. The death risk from cardiovascular diseases was over 3.0 times higher than in general population. The relevant risk ratio was found over 5-times higher for coronary heart disease, which was unlike to result from the differences in death ascertainment between diabetics and the city dwellers. The all-causes ratio of death and cardiovascular diseases was the same for women and men but it was selectively higher for females than males group for coronary heart disease and cerebrovascular diseases, and for males 50% higher for atherosclerosis and other heart diseases. The highest cumulation of risk factors was observed for deaths from cardiovascular diseases, and coronary heart disease. There were risk factors typical for cardiovascular disease and typical for poor metabolic control of diabetes (hyperglycaemia, glucosuria) and presence of complications of diabetes (nephropathy).

The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex.

Organisms in many phyla determine sexual fate by distinguishing one X chromosome from two. Here we use the model organism Caenorhabditis elegans to dissect such an X-chromosome-counting mechanism in molecular detail. In this nematode, several genes on the X chromosome called X signal elements communicate X-chromosome dose by controlling the activity of the sex-determination gene xol-1. xol-1 specifies male (XO) fate when active and hermaphrodite (XX) fate when inactive. The only X signal element described so far represses xol-1 post-transcriptionally, but xol-1 is repressed in XX animals by transcriptional and post-transcriptional mechanisms. Here we identify a nuclear-hormone-receptor homologue, SEX-1, that regulates the transcription of xol-1. We show that sex-1 is vital to X-chromosome counting: changing sex-1 gene dose in XX or XO embryos causes sexual transformation and death from inadequate dosage compensation (the hermaphrodite-specific process that equalizes X-gene expression between the sexes). The SEX-1 protein acts directly on xol-1, associating with its promoter in vivo and repressing xol-1 transcription in XX embryos. Thus, xol-1 is the direct molecular target of the primary sex-determination signal, and the dose of a nuclear hormone receptor helps to communicate X-chromosome number to determine nematode sex.

[Risk factors of the incidence of late vascular complications of diabetes]. / Czynniki ryzyka zapadalnosci z powodu powiklan naczyniowych cukrzycy.

From the follow-up examination of 1329 out of 4420 type 2 (non-insulin-dependent) diabetes followed for 17 years, the incidence of micro and macrovascular complications (proteinuria and nephropathy, symptoms of leg vascular disease, ischemic heart disease, and cerebrovascular events, was estimated and related to the levels of baseline-risk variables using logistic regression. For new cases of proteinuria and heavy proteinuria, hyperglycemia was the common predictor (alongside diastolic hypertension, smoking and overweight); hyperglycemia and glycosuria were among significant predictors of leg vascular disease (with duration of diabetes, smoking, male sex, diastolic hypertension, and proteinuria). On the other hand, systolic hypertension and male sex prevailed among factors predicting both ischemic heart disease (with high cholesterol and overweight), and stroke. The data confirm the higher involvement of diabetic milieu in micro than macrovascular incidents, with diabetic foot disease placed in between.

[Mortality of diabetic patients in Warsaw--22 year prospective observation (1973/74-1995). I. Mortality of diabetic patients with type 2 diabetes (non-insulin-dependent-diabetes)]. / Umieralnosc chorych na cukrzyce w Warszawie--22-letnia obserwacja prospektywna (1973/74-1995). Czesc I. Umieralnosc chorych na cukrzyce typu 2 (insulinoniezalezna).

In the period 1973/74-1995 a prospective observation was carried out on 4420 diabetic patients (1990 males and 2430 females) aged 30-68 years, with type 2 (non-insulin dependent diabetes) of 1-10 years duration. During the 22-years period nearly 80% of initial cohort died. The risk of death were 2-times higher in diabetes than in the samples of general population observed at the same time. The death risk from cardiovascular disease were over 3-times higher than in general population. The relevant risk ratio has been found over 5-times higher for coronary heart disease, which were unlike to results from the differences in death ascertainment between diabetics and the city dwellers. The all-causes ratio of death and cardiovascular diseases were the same for women and men but it was selectively higher for females then males group for coronary heart disease and cerebrovascular diseases. Among diabetic cohort the risk of death was also higher for neoplasms, especially in women.

[Mortality of diabetic patients in Warsaw--22 year prospective observation (1973/74-1995). II. Mortality of patients with type I diabetes (insulin-dependent-diabetes)]. / Umieralnosc chorych na cukrzyce w Warszawie--22-letnia obserwacja prospektywna (1973/74-1995) czesc II. Umieralnosc chorych z cukrzyca typu 1 (insulinozalezna).

During the follow-up 1973/74-1995 years 171 subjects with type 1 (insulin dependent diabetes) (105 males and 66 females) aged 18-30 years died 31.6% (32.4% males and 30.3% females). The relative risk of mortality for all causes in the compared to the general population was 5.0 (3.5 for men and 7.5 for women). Almost 30% deaths were from renal disease, 17% from ischemic heart disease, and 3 death in women from carcinoma of breast.

Epidemiology of non-insulin-dependent diabetes mellitus and its macrovascular complications. A basis for the development of cost-effective programs.

Non-insulin-dependent diabetes mellitus is a major health problem in developed countries. The descriptive epidemiology of this disease and its cardiovascular complications are reviewed, and insulin resistance is identified as a common risk factor for both of them. The requirements for cost-effective programs to modify insulin resistance to prevent this disorder and its cardiovascular complications are discussed.

xol-1 acts as an early switch in the C. elegans male/hermaphrodite decision.

xol-1 is the earliest-acting gene in the known hierarchy that controls C. elegans sex determination and dosage compensation. We show that the primary sex-determining signal (the X/A ratio) directs the choice of sexual fate by regulating xol-1 transcript levels: high xol-1 expression during gastrulation triggers male development, whereas low expression at that time permits hermaphrodite development. Inappropriately high xol-1 expression causes hermaphrodites to activate the male program of development and die from a disruption in dosage compensation. These results demonstrate that xol-1 functions as an early developmental switch to set the choice of sexual fate and suggest that assessment of the X/A ratio occurs only early in embryogenesis to determine sex. Moreover, sdc-2, a gene that must be repressed by xol-1 to ensure male development, may be a direct target of negative regulation by xol-1.

Translational readthrough at nonsense mutations in the HSF1 gene of Saccharomyces cerevisiae.

The HSF1 gene of Saccharomyces cerevisiae directs the synthesis of the heat shock transcription factor, HSF. The gene is essential; disruption mutations are lethal. Using a plasmid shuffle screen, we isolated mutations in the HSF1 gene after in vitro mutagenesis of plasmid DNA with hydroxylamine. From a collection of both conditional (temperature-sensitive) and unconditional lethal mutations, we recovered mutations that map exclusively to the 5' half of the gene. All are nonsense mutations, including conditional mutations that map 5' to the portion of the HSF1 gene that encodes the DNA-binding domain of the transcription factor. For one such mutation, we demonstrated that the nonsense mutation is subject to translational readthrough, even though there are no known nonsense suppressors in the genetic background of our strain. Our results suggest that the HSF protein is highly tolerant of amino acid changes, a conclusion that is consistent with the very low degree of evolutionary conservation among HSF proteins. Our results also suggest that translational readthrough occurs with moderate efficiency in yeast, particularly when the terminator codon is followed immediately by an A or C residue. This result illustrates that the inference of gene function from mutant phenotype depends critically upon the analysis of a true null allele, and not merely an amber or ochre allele.

[Cetirizine for treating allergic seasonal rhinitis]. / Cetyryzyna w leczeniu alergicznego sezonowego niezytu nosa.

In 14 persons suffering from allergic, seasonal rhinitis the efficacy of 14-days treatment of cetirizine (Zyrtec 10 mg/day) was evaluated. The study was performed in double blind randomised method. Cetirizine was significantly more effective than placebo in reducing the clinical symptoms of rhinitis near in 60% patients. The improvement of nasal mucosa state in laryngological investigation was observed in patients who were better clinically. The inhalatory challenge test with histamine in 9 patients was positive and after cetirizine treatment the bronchial hyperreactivity disappeared.

[Psycho-social precursors of arterial hypertension in men and women in light of clinical cohort studies]. / Psychospoleczne prekursory nadcisnienia tetniczego u mezczyzn i kobiet w swietle badania kliniczno-kohortowego.

Following two prevalence studies of arterial hypertension carried out at 5-year interval on 6487 adult inhabitants of Ochota District, Warsaw, screening for new cases was performed at the end of the five- or ten-year observation period. Interviews were collected from 472 incident and unknown prevalence cases and 499 randomly chosen non-cases regarding social and work conditions, selected behavioral traits and personal habits. The risk of hypertension was more closely associated with blue collar social status, poor economic self-assessment and repetitive type of work in women than men. In males, but not females, higher risk was connected with expressed anger followed by feeling of guilt, but no otherwise suppressed anger was predictive of hypertension. In both sexes the incidence of the disease was higher among people reporting less life events, and with less involvement in the household and/or professional activities.

Risk factors of cardiovascular death in diabetic patients.

In 1974 a cross-sectional study was conducted on 4591 out-patients (2095 males and 2496 females) aged 18-67 years, with diabetes of 1-10 years duration, and cardiovascular fatalities followed for 10 years. A multiple logistic regression was then performed on total cardiovascular deaths, deaths from ischaemic heart disease, and from stroke on selected baseline variables related to the course and control of diabetes, selected symptoms of macroangiopathy, and other risk factors, separately for insulin-treated and non-insulin-treated patients. Hyperglycaemia, proteinuria, arterial hypertension, various symptoms of ischaemic heart disease, age, and current cigarette smoking were found to be important predictors of cardiovascular mortality, more so in non-insulin-treated than in insulin-treated patients. Proteinuria and arterial hypertension carried a greater risk in females than males, but the opposite was true for the signs and symptoms of ischaemic heart disease. Relative body mass was found to correlate inversely with probability of cardiovascular death among insulin-treated males but not in non-insulin-treated males, whereas duration of diabetes was a significant factor only among non-insulin-treated females.

[Gradenigo syndrome with atypical course]. / Zespól Gradenigo o nietypowym przebiegu.

The Gradenigo syndrome in course of the nasopharyngeal cancer was described. The diagnostic problem was discussed. The primary symptoms were usually the chronic otitis and neck lymphadenitis.

[Factors determining the presence and predicting the development of diabetic retinopathy]. / Czynniki okreslajace obecnosc i zapowiadajace wystapienie retinopatii cukrzycowej.

In a group of 329 diabetics aged 35-56 years with diabetes duration 1-30 years 134 cases were found diabetic retinopathy (40.7%). After 7 years funduscopy was repeated in 136 out of 248 patients and 50 new cases of retinopathy were disclosed. After multivariate analysis it was found that retinopathy was associated most closely with diabetes duration, while arterial hypertension was most surely predicting during 7 years future retinopathy, particularly in the case of higher level of glycosylated haemoglobin at the final examination.

[Mortality among patients with diabetes mellitus in Warsaw--a 10-year prospective study]. / Umieralnosc chorych na cukrzyce w Warszawie--10-letnia obserwacja prospektywna.

In the period 1973/74-1983 a prospective observation was carried out on 4591 out-patients (2095 males and 2496 females) aged 18-68, with predominantly non-insulin treated diabetes of 1-10 years' duration. During the ten years period over a third of initial cohort died. Age-standardized mortality rate was twice that for the general population of Warsaw for the median year 1978. The risk of death rose with decreasing age, especially in females. The most frequent causes of death were cardiovascular diseases, particularly coronary heart disease, standardized mortality ratios amounting to 2.7 and 2.4 respectively. Among diabetic cohort the risk of death was also higher for nephritis, nephrosis, cirrhosis of the liver and pneumonia. No excess death rate could be found for tuberculosis, malignant neoplasms, and diabetes itself. Diabetic patients were less frequently exposed to accidental deaths than the general population of Warsaw. The mortality diabetic patients in Warsaw was similar to that seen in most of the developed countries with the exception of the higher mortality due to cirrhosis of the liver and smaller due to accident, trauma and poisoning.

[Mortality risk factors in cardiovascular diseases in patients with diabetes mellitus in Warsaw--a 10-year prospective study]. / Czynniki zagrozenia zgonem z powodu chorób ukladu krazenia u chorych na cukrzyce w Warszawie--10-letnia obserwacja prospektywna.

A prospective study was made in the years 1973 through 1983 on mortality among 4591 patients (2095 men and 2469 women) with usually noninsulin dependent diabetes, of 1-10 years duration. The anamnestic data and examination parameters obtained during a cross-sectional investigation served as the prognostic changeables (risk factors) to assess the mortality due the most frequent circulatory diseases. The applied model of the logistic regression allowed an attempt of the assessment of their independent effect. Analysis regarding the sex and the methods of diabetes treatment was done in four groups of mortality causes classified according to the VIII Revision of the International Classification of Disease. Injuries and Causes of Death: 1. Cardiovascular system diseases. 2. Ischaemic heart diseases. 3. Other diseases of the cardiovascular system. 4. Vascular diseases of the brain. The quantitative and qualitative effect of the arbitrarily chosen factor of death risk was of varying importance and was related to the sex and the methods of the hypoglycemising treatments. The effect of ageing was an independent factor of death risk among all analysed causes of mortality in both sexes independent from the methods of the hypoglycemising treatment with the one exception of women treated with insulin who died of stroke. Generally however, the ageing factor showed a greater prognostic value in patients treated with insulin. Hypertension, especially if marked, showed to have the most prognostic value among the all analysed factors of death-risk especially in patients on oral antidiabetics. The risk in this group was due mainly to the cerebral stroke, to a lesser degree to the "other" diseases of the circulatory system, and to the all diseases of the circulatory system but to the least degree it was related to the ischaemic heart disease, in both sexes. Among insulin treated diabetics the hypertension was a death-risk of most importance in men usually due to the vascular brain disease and other diseases of the cardiovascular system but to a lesser degree to the circulatory diseases, as a whole. In women however the marked hypertension increased the death-risk in patients with coexisting circulatory disease, not a particular one, but as a whole. Albuminuria had a pronounced prognostic value, especially if massive, in both types of diabetes, mainly, however, among women who died of any cardiovascular causes.(ABSTRACT TRUNCATED AT 400 WORDS)