Early prognostic biochemical indicators of fulminant hepatic failure

This article reviews related studies from the authors' laboratory, which focus on the regulation of vascular Na+,K+-ATPase in hypertension. Earlier studies, including the authors', suggested that Na-pump activity in cardiovascular tissues is subject to regulation during hypertension; most of these studies report a stimulation of the vascular enzyme during established stages of hypertension. To test hypothesis that in vascular smooth muscle, strain resulting from elevated pressure may be a signal initiating a cascade of events leading to increased expression of Na+,K+-ATPase, the authors used cell culture and the Flexercell Strain Unit to apply cyclical stretch to rat aortic smooth muscle cells (ASMC) for several days. These studies demonstrated that mechanical strain induces the upregulation of both the alpha-1 and alpha-2 subunits of Na+,K+-ATPase. Mechanisms underlying these changes appear to involve a transient increase in intracellular sodium entering the cell through stretch-activated channels. Calcium entering the cell via L-type channels did not affect stretch-induced upregulation of the alpha isoforms. In addition, protein kinase C inhibition resulted in inhibition of the Na-pump during stretch, but not under nonstretch conditions. The authors conclude that the stretch component of vascular pressure upregulates the Na+,K+-ATPase catalytic subunits. Intracellular sodium may be a signal for this regulation. In addition, phosphorylation by PKC may be important in stretch-induced short-term regulation of the vascular Na-pump.     

Diagnostic and prognostic significance of arterial pressure in late toxemia in pregnancy

Manganese content in blood sera of healthy subjects fluctuates within the interval of 0.008 mkg/ml to 0.032 mkg/ml--hence the requirement of especially sensitive methods for manganese determination. Atom-absorption methods are very suitable in this case because a minimal preparation of the sample is required. The authors intended the elaboration of a direct atom-absorption method, tracing manganese content in blood and urine. Manganese content in blood serum is rather close to the detectable minimum for manganese in its determination with the applied two-beam atom-absorption spectro-photometer. In the present work, the results from the prophylactic examinations of workers are presented, being in occupational contact with manganese (occupational-pathological screening) as well as from a control group of practically healthy volunteers--blood donors. Values in the interval 0.1017--0.032 mkg/ml with a standard deviation of 0.003 mkg/ml were obtained for the control group. The group of the workers examined, being in contact with manganese aerosols has an average value of 0.034 mkg/ml. Eighty eight per cent of all examined are in the interval from 0.01--0.05 mkg/ml. The rest 12 per cent work in shops where manganese elimination is higher. The method proposed is productive (up to 100 manganese determinations in diluted 1:1 serum per hour).     

Clinical and pathological significance of numerical aberrations of chromosomes 11 and 17 in colorectal neoplasms

Numerical chromosome aberrations by interphase cytogenetic analysis have been reported in a few samples of colorectal neoplasms. No studies have defined a distinct relationship between these aberrations and clinicopathological features. To investigate the chromosome aberrations as a marker of invasiveness or prognosis, we conducted an interphase cytogenetic study using fluorescence in situ hybridization and examined 142 colorectal neoplasms consisting of 15 adenomas and 127 cancers. The target chromosomes were chromosomes 11 and 17. We also evaluated the nuclear DNA content as detected by flow cytometry, analyzed the relationship between the frequency of aneusomy and clinicopathological features, and examined the survival rate in these patients. The loss of chromosome 11 was observed in 31% of adenomas, whereas in cancers DNA aneuploidy was observed in 63% of cases, a gain of chromosome 17 was observed in 63% of cases, and a gain of chromosome 11 was observed in 42% of cases. Numerical chromosome aberrations in diploid DNA were also observed. Increased depth of invasion (>/=T3) and advanced Dukes' stage (>/=B) of malignant tumors were associated with a higher frequency of a gain of chromosome 11 (P < 0.01 and P < 0.05, respectively). Increased depth of invasion (>/=T2) in cancers was associated with a higher frequency of a gain of chromosome 17 (P < 0.05). Multivariate analysis of postoperative survival showed that a loss or gain of chromosome 11 was independently associated with a poor prognosis (P < 0.05). Numerical chromosome aberrations appear prior to the alteration of nuclear DNA content as detected by flow cytometry and influence the progression of colorectal cancers. Aneusomy of chromosome 11 is associated with poor postoperative prognosis of primary colorectal cancers.     

Diagnostic significance of telomerase activity and telomere length in endoscopic sample of colorectal cancer

Telomeres are located on both ends of individual chromosomes in eukaryotes. It has been reported that telomerase activity and telomere reduction can be detected in most human cancers. We examined telomerase activity and telomere length in colorectal cancer tissues obtained by colonoscopy. Telomerase activity was examined by the TRAP (telomeric repeat amplification protocol) assay and was detected in 21 of 26 (81%) primary colorectal carcinoma tissues. Two of 9 (22%) colorectal polyp were telomerase positive. Telomere length was analyzed by Southern blotting and there was reduction in telomere lengths in 12 of 15 (80%) primary colorectal carcinoma and 3 of 6 colorectal polyp, compared to the corresponding normal colonic mucosa. Therefore, telomerase activity and telomere length may serve as an useful tool for preoperative cancer diagnosis.     

Diagnostic electron microscopy of neoplasms

OBJECTIVE: We describe a patient with a prolonged and severe hypercapnia occurring during an episode of status asthmaticus induced by ophthalmic instillation of carteolol. SETTING: Prehospital Emergency Medical Service and Pulmonary Intensive Care Unit in a university hospital. PATIENT: A 35-year-old female developed an acute asthma attack while at home, which required advanced life support. INTERVENTION: On hospital admission, arterial blood gases revealed a PaCO2 of 208 mmHg. Hypercapnia persisted with a PaCO2 of more than 190 mmHg for 10 h, with pH always less than 7.00. The patient was finally discharged after 26 days without sequelae. CONCLUSION: This case illustrates the cerebral and cardiovascular tolerance of severe and prolonged hypercapnia associated with major acidosis.     

Clinical and prognostic aspects of adrenocortical neoplasms in childhood

BACKGROUND: A retrospective study of 54 children was undertaken to define the clinical presentation and secretory patterns of adrenal tumors and to evaluate the outcome of surgical resection and medical therapy. PROCEDURES: Different factors were studied in univariate and multivariate analysis by using the Cox proportional hazard model. RESULTS: Median age at diagnosis was 4 years. Boys and girls were affected equally. The disease was revealed by virilization (61%) or by a palpable mass (39%) with a 0.1-5.5 year delay from initial symptoms. At initial examination, we found that 76% of children were virilized. Ninety-four percent of the tested tumors secreted androgens, which were associated with glucocorticoids in 36%. Adrenal tumors in children were smaller than in adults. Half of them measured less than 10 cm. There were recurrences in 40% of children. The survival rate at 5 years was 49%, 70% if resection was microscopically complete and 7% if not (P < 0.001). CONCLUSIONS: In children, rare adrenal tumors have different diagnostic and prognostic characteristics than in adults; however, recurrences remain frequent. The efficacy of chemotherapy, mainly o,p'-DDD (Mitotane), remains to be evaluated in comparative trials.     

Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance

To evaluate the prognostic significance of immunohistochemically detected p53 and Bcl-2 proteins in colorectal cancer, tissue sections from 238 paraffin-embedded colorectal carcinomas were immunostained for p53 (MAb DO-7 and CM-1 antiserum) and Bcl-2 (MAb Bcl-2:124). Staining patterns were assessed semiquantitatively and correlated with each other and with sex, age, tumour site, Dukes' classification, tumour differentiation, mucinous characteristics, lymphocyte and eosinophilic granulocyte infiltration, and patient survival. In our series, 35% of carcinomas showed no nuclear staining and 34% (DO-7) to 40% (CM-1) showed staining in over 30% of tumour cell nuclei. A majority of carcinomas that had been immunostained with CM-1 showed cytoplasmic staining, but this was not observed with DO-7. With respect to Bcl-2, 51% of tumours were completely negative, 32% displayed weak and 15% moderate staining; only 3% showed strong positive staining. No evidence was found for reciprocity between Bcl-2 expression and nuclear p53 accumulation. From 13 cases containing tumour-associated adenoma, four were Bcl-2 negative in premalignant and malignant cells, in another four cases these cells showed similar staining intensities and in the remaining cases only the malignant colorectal cells were Bcl-2 negative. Therefore, our data indicate that Bcl-2 is dispensable in the progression towards carcinoma. Except for an association between nuclear p53 accumulation and mucinous tumours (P = 0.01), no significant correlation was found between the clinicopathological parameters mentioned above and immunostaining pattern of (nuclear or cytoplasmic) p53 or Bcl-2.     

Diagnostic and prognostic decision support systems

Diagnostic decision support systems provide a quantitative evaluation of diagnostic evidence and the capability to combine diagnostic evidence in such a manner that a numeric measure of certainty in a final diagnostic recommendation results. Generally, expert systems serve to establish a diagnostic decision, inference networks allow a detailed analysis of the diagnostic value of diagnostic clues, case-based reasoning systems are designed to provide a prognostic assessment targeted to an individual patient. In all of these systems, symbolic information, i.e., traditional diagnostic, linguistic terms and concepts are processed and quantitatively evaluated.     

Role of p53 gene in colorectal neoplasms

A prospective study on the role of the p53 gene in sporadic colorectal neoplasms is presented and the level of mutant p53 protein was measured in the tissue removed during colonoscopy from: patients previously operated for colorectal malignant neoplasms, patients with active neoplasms, first degree relatives and during regular checks. 72% of patients with an active tumour showed a positive p53 and 38% in follow-up checks. Longer follow-up periods and a major number of patients are necessary to assess the prognostic importance of the p53 protein.     

Diagnostic and prognostic significance of an increase in fractional protein clearance ratio before and during rejection of renal transplant

We measured prospectively changes in fractional protein clearance ratio (CPr/CCr) in 21 live-related (LR) and 41 cadaver donor (CD) renal transplants before and during onset of first rejections. Fifty-three recipients manifested a rejection within the first post-transplant month. Fractional protein clearance increased in all patients during rejection. An increase in CPr/CCr prior to other evidence of impending rejection, and therefore clinically useful, required at least a 10-day rejection-free interval dated from onset of diuresis (whether diuresis was immediate or delayed by acute tubular necrosis (ATN)). Twenty-three of 25 nonantilymphocyte globulin (ALG)-treated CD transplants manifested clinical and laboratory signs of the first rejection episode prior to the 10th day of diuresis compared with 5 of 21 LR and none of 16 ALG-treated CD transplants. Persistence of elevated CPr/CCr despite treatment forecast graft loss (11 of 13), whereas a decrease in this ratio was associated with ultimate reversal of the rejection process.     

Expression of CuZn- and Mn-superoxide dismutase in human colorectal neoplasms

Decreased intracellular SOD protein levels and activity have been related with malignancy in the past. To investigate their relevance in the carcinogenetic process in the colon, we determined quantitatively CuZn-SOD and Mn-SOD levels and total SOD activity by histochemical means in human normal colorectal mucosa, adenomas, and carcinomas. Protein levels and activity were significantly decreased in carcinomas. CuZn-SOD protein levels, but not Mn-SOD levels or total SOD activity were related with differentiation grade and to a lesser extent with Dukes stage. Moderately differentiated carcinomas and Dukes stage A carcinomas showed lowest levels. Some carcinomas expressed elevated levels of CuZn-SOD and this was an indication of poor survival. It is concluded that decreased SOD expression is not a prognostic marker and seems to be a secondary phenomenon rather than directly linked with the carcinogenetic process.     

Early biochemical indicators of renal damage in arterial hypertension

The demonstration that stains reduce the risk of cardiovascular diseases, in both secondary and primary prevention trials, led to the recent publication of sophisticated pharmaco-economical studies. A lot of factors may influence the cost-effectiveness ratio of the pharmacological intervention, especially the mode of calculation of various costs, the initial level of cardiovascular risk of the patients and the medico-economical particularities of each country. What so ever, available studies appear to justify the use of statins in secondary prevention, i.e. in coronary patients, even those with only a moderate hypercholesterolaemia, and, in primary prevention, i.e in hypercholesterolaemia individuals with obvious high risk of cardiovascular disease.     

Correlation between biochemical indicators of physical fitness and age

16 men in the average age of 23.7 years and 24 juniors in the average of 17 years, ice-hockey players, were investigated. A significant negative correlation between the physical fitness and indicators of lipoprotein metabolism were found. This correlation proved the significance of the intensity of physical activity as a factor decreasing the risk factors of atherosclerosis. Significantly higher levels of triacylglycerols and significantly lower HDL-cholesterol were found in men when compared with the juniors. The comparison of two age categories which were subjected to regular long-term physical activity of high intensity, proved the influence of the age of ice-hockey players who had been trained under the same conditions. Both quantitative and qualitative changes in lipoprotein metabolism proved the increase in atherogeneous risks with the increasing age. (Tab. 7, Ref. 14.)     

Diagnostic and prognostic relevance of malignancy-associated changes in cervical smears

OBJECTIVE: For approximately 15 years, malignancy-associated changes (MACs) have been consistently found by means of high-resolution cytometry in different tissues, especially in visually normal appearing cervical cells. Their biologic nature is not yet fully understood. The aim of this investigation was to assess the expression of MACs in cervical smears and to evaluate their prognostic relevance. STUDY DESIGN: This study was performed on normal intermediate cells obtained from 53 cytologically positive and 78 cytologically negative cervical smears. From a second sample, 31 cases showing negative cytology were selected for a prospective longitudinal study. Densitometric and texture features were generated, and MACs were described on the basis of multivariate discriminant analysis. RESULTS: Discrimination between positive and negative cases was possible, with a correct classification rate of approximately 80%. After a mean period of 29.5 months, we noted no statistically significant increase in the incidence of cervical intraepithelial neoplasia in the group of healthy but MAC-positive women as compared to those who were MAC negative. CONCLUSION: MACs were constantly expressed in the epithelium of the cervix. Although their prognostic relevance remains unclear, MACs play an important role in the effort to automate cervical cytology.