Forensic necroptic epidemiology -- a useful method for the evaluation of renal, cardiac and cerebral lesions. Can it represent an addition to the information provided by clinical studies?

Our paper reviews the value of necroptic epidemiology in the evaluation of renal, cardiac and cerebral lesions. The necroptic epidemiology studies performed on American war casualties from Korea and Vietnam had practical implications in the prophylaxis of atherosclerosis in young age groups. The special interest they initially raised has been diminished by the advance of clinical studies that are nowadays dominant in the field of epidemiology. Given the fact that for the evaluation of certain diseases, such as chronic kidney disease, the morphological criterion is useful for the diagnostic, necroptic epidemiology can complete the epidemiological data provided by clinical studies. The use of data offered by forensic necroptic epidemiology can represent a reliable method for evaluating the epidemiology of certain diseases and of their complications.

The immunohistochemical expression of the p53-protein in gastric carcinomas. Correlation with clinicopathological factors and survival of patients.

BACKGROUND: P53-tumor suppressor gene has an essential role in controlling cell cycle and initiating carcinogenesis. In the case of gastric cancer, the role of p53-protein accumulation as prognostic factor is controversy. Various results are due to the different methods of study regarding patients' selection, immunohistochemical techniques used and the quantifying systems for immunoreactions. AIM: Assessment of p53-immunohistochemical expression in 61 patients with gastric carcinomas and the correlation with clinicopathological factors (gender, age, location, macroscopic, and histological type, degree of tumor differentiation and TNM-stage) and patients' survival. MATERIAL AND METHODS: From the total number of 265 patients (186 males and 79 females) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of five years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). We used the monoclonal antibody DO7 that detects the wild and mutant form of p53-protein, by EnVision technique and DAB-visualization. We considered positive reaction only in the presence of brown staining of the nuclei. RESULTS: P53-immunoreactions were positive in 25 gastric cancers (41%). We obtained positive stainings in 41.9% cases in men and 38.9% women. We found positive p53-immunoreactions in all the carcinomas developed in the upper third of the stomach (100%), in 53.3% of the corporeal tumors, 50% of the pangastric tumors; according to Lauren's classification, we noticed a significantly increased immunoreaction of p53 in the intestinal-type carcinomas. Among histological types, papillary, mucinous, anaplastic and tubular adenocarcinomas presented a relatively increased percentage of p53-positive immunoreactions. P53-positive stainings are more frequently encountered in moderate/poor differentiated carcinomas and those associated with lymphovascular invasion; according to pT- and pN-stage, we remarked a significantly increase of the number of p53-positive cases (p=0.02291 and p=0.038264). Five-year survival rate for patients with p53-positive carcinomas was significantly lower in comparison to the patients p53-negative (8% vs. 22.2%, p=0.0326). CONCLUSIONS: Immunohistochemical evaluation of p53-protein represents in our study an important prognostic factor, allowing the selection of a group of patients with an aggressive therapeutic indication, such as extensive lymphadenectomy and adjuvant chemotherapy.

Gastric cancer: correlation between clinicopathological factors and survival of patients (III).

PURPOSE: The purpose of this study was to identify the clinicopathological factors that influence the prognosis of patients having undergone surgery for gastric cancer. The analysis of the potential prognosis factors has included in this study parameters concerning the patient (sex, age), as well as parameters related with the tumor (histological type according to the WHO classification; degree of tumor differentiation; tumor location; stage of disease; pT and pM parameters according to the TNM classification of AJCC/UICC). MATERIAL AND METHODS: From the total number of 265 patients (186 men and 79 women) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of 5 years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). RESULTS: The studied group consisted of 61 patients (43 men and 18 women), with ages between 30 and 80 (average age = 59.34 years). According to the maximum level of tumor invasion we identified: pTis - one case (1.6%); pT1 - four cases (6.6%); pT2 - nine cases (14.7%); pT3 - 17 cases (27.9%); most gastric cancers were included in the pT4 category (49.2%). We identified 43 gastric carcinomas with metastases in regional lymph nodes (70.5% of the cases). According to the number of lymph nodes involved: pN0 - 18 cases (29.5%); pN1 - 16 cases (26.2%); pN2 - 23 cases (37.7%); pN3 - four cases (6.6%). Distance synchronous metastases were present in 14 gastric carcinomas (pM1 - 23% of the cases), nine cases with hepatic metastases and five cases with distance peritoneal disseminations. Classification of gastric carcinomas: we identified one single case listed in the 0 stage, three cases in the IA stage, five cases in the IB stage, seven cases in the II stage, 11 cases in the IIIA stage, eight cases in the IIIB stage, and 26 cases in the IV stage. From the total of carcinomas, stage IV consisted of the greatest number of tumors, representing 42.6%. We generally remarked the increase of the number of cases in advanced stages. CONCLUSIONS: In the studied group, we noted a great number of gastric carcinomas diagnosed in stages T3 and T4 (77.1% of cases). Cardial tumor locations and gastric stump locations, as well as "signet-ring" cell and undifferentiated carcinomas prove to be aggressive, being diagnosed in advanced stages. 70.5% of gastric neoplasms presented lymph node metastases, most cases representing pN2 tumors (37.7%). 23% of neoplasms studied presented distance metastases at the time of diagnosis. We noted a significant correlation between the degree of tumor differentiation and the level of invasion, as well as the presence of distance and lymph node metastases. Survival at 5 years of patients included in the study was correlated significantly with the level of tumor invasion, the presence of lymph node and distance metastases, and the TNM stage.

The effect on proteinuria and urinary NAG of treatment with meloxicam in chronic glomerular disease patients--a preliminary study.

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) that primarily has an antiproteinuric effect and is used for the treatment of chronic glomerular diseases. In chronic glomerular disease (CGD), proteinuria is involved in the production of tubulo-interstitial lesions and has an important role in their progression. CGD improves with steroid therapy and immunosuppression. In the case of a favorable outcome, a reduction in proteinuria is also attained. In some situations, this therapy is prohibited, requiring alternative medication. NSAIDs are one class of these alternative drugs; in addition to having anti-inflammatory actions, they also have antiproteinuric effects. The aim of the study has been to assess the effect of the anti-inflammatory treatment with meloxicam upon proteinuria as well as upon tubular lesions by determining urinary NAG in its dynamics. The study was performed on 12 patients with CGD, 6 of them with nephrotic syndrome. On all patients we administered treatment with meloxicam 15 mg/day, 30 days. On all patients we performed proteinuria and urinary N-acetyl b D glucosaminidase (NAG) at the beginning, after 7 days and after 30 days of treatment. A 24-hour urine collection was taken from all patients. The urinary protein concentration was determined with the use of the Dimension (Dade Behring, Inc., Newark, DE, USA) clinical chemistry system UCFP method. We found a decrease of proteinuria under treatment from 2.85 +/- 1.69 g/24h to 1.53 +/- 0.83 g/24h, which was significantly lower, compared to the initial measurement (p = 0.01878). After 30 days of treatment with meloxicam, urinary NAG decreased from 10.6 +/- 12.56 U/g creatinine to 6.44 +/- 7 U/g, a decrease that was statistically non-significant. We observed a strong correlation between initial urinary NAG and initial proteinuria ri = 0.924, p < 0.001 and between final urinary NAG and final proteinuria rf = 0.856, p < 0.001. Our study revealed the favorable effect of meloxicam on patients with CGD on a 30-day treatment phase reflected on the evolution of proteinuria. Only in one case we did reveal a possible deleterious effect of this treatment. The assessment of the effect on tubulo-interstitial lesions in this short treatment period through urinary NAG assessment indicated only a modest and statistically non-significant response. We consider that meloxicam can be a useful drug in the treatment of proteinuric glomerular diseases.

Gastric cancer: correlation between clinicopathological factors and survival of patients. II.

PURPOSE: The purpose of this study was to identify the clinicopathological factors that influence the prognosis of patients having undergone surgery for gastric cancer. The analysis of the potential prognosis factors has included in this study parameters concerning the patient (sex, age), as well as parameters related with the tumor (macroscopic aspect of the tumor according to the Borrman's classification, histological type according to the WHO and Lauren's classifications, degree of tumor differentiation, tumor location, stage of disease, pT and pM parameters according to the TNM classification of AJCC/UICC). MATERIAL AND METHODS: From the total number of 265 patients (186 men and 79 women) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of 5 years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). RESULTS: The studied group consisted of 61 patients (43 men and 18 women), with ages between 30 and 80 (average age = 59.34 years). We have identified five papillary adenocarcinomas (8.2%), 28 tubular adenocarcinomas (46%), 17 "signet-ring" cell carcinomas (27.8%), eight mucinous adenocarcinomas (13.1%), and three undifferentiated or anaplastic carcinomas. Most gastric carcinomas examined were included in the category of poorly differentiated carcinomas (63.9%). According to the Lauren's classification, we have identified 38 intestinal type gastric carcinomas (62.3%), 17 diffuse type carcinomas (27.9%), and six mixed carcinomas (9.8%). We have identified aspects of lymphovascular invasion in 38 cases (62.3%). CONCLUSIONS: "Signet-ring" cells carcinomas, and the anaplastic ones, prove in our study to be extremely aggressive histological forms, characterized through low rates of survival. We remarked a significant correlation between the degree of tumor differentiation and survival of patients, the values recorded being significantly lower in medium and poorly differentiated carcinomas (p = 0.00871194 FS). Average survival, calculated in months, is significantly lower in patients with diffuse type carcinomas (11.3 months), in comparison with patients presenting intestinal type carcinomas (20.4 months) (p = 0.0415 S). There is a direct proportional relationship between the lymphovascular invasion and the number of positive lymph nodes. Survival after 5 years decreases significantly in the presence of lymphovascular invasion.

Conventional treatment or epidural blood patch for the treatment of different etiologies of post dural puncture headache.

Post dural puncture headache (PDPH) represents a complication of anesthesia (with an increased incidence in obstetric patients) or as the consequence of a diagnostic lumbar puncture. The aim of the present study was to evaluate the efficacy of the epidural blood-patch (EBP) versus the conventional medical treatment of post-anesthetic headaches also including the PDPH following a diagnostic puncture, a category of patients rarely referred to the anesthesia consultation in our hospital because it was believed that they might have equal benefit from conventional measures due to the smaller size of needles used. We studied in a prospective, randomized, double-blinded manner 32 obstetric and non-obstetric patients with PDPH having the onset of the symptoms 24 hours before the inclusion in the study. The patients were randomly divided in two groups: group A (16 patients) receiving conventional treatment (oral and intravenous fluid replacement, non-steroidal anti-inflammatory drugs--NSAIDs--, caffeine) and group B (16 patients) in whom an epidural blood-patch was performed. The intensity of the headache was evaluated using a visual analogue scale (VAS) from 0-10, before, 2 hours and 24 hours after the EBP. There were no statistical differences concerning the demographic data and the cause of PDPH between the groups (p > 0.05). The intensity of PDPH was similar before performing the EBP (p > 0.05), with a value on VAS of 8.2 +/- 1,4. in group A and 8,0 +/- 1.6 in group B. Two hours after the treatment, the intensity of headache on VAS diminished extremely significant (p < 0.0001): in group B the value was 1.0 +/- 0,18 versus 8.2 +/- 1.4 in group A. The difference recorded after 24 hours remained statistically significant (p < 0.0001): the VAS scores were 0.7 +/- 0,16 and 7.8 +/- 1.2 respectively. The epidural blood patch represents the first choice treatment of PDPH no matter the etiology, being significantly superior to the conventional treatment which did not affect pain scores. In severe PDPH there is no reason to delay the EBP more than 24 hours after the diagnosis as all except two patients of the conventional treatment group required blood patching following the study period.

Medical informatics education for "allied" profiles.

Medical informatics education should be adapted for each speciality of "allied professions". In this paper we try to share from our experience with students of several profiles: medicine, dentistry, pharmacy, physio-kineto-therapy, clinical laboratory, dentistry techniques and stomatological prophylaxis.

Modeling and simulation in molecular pharmacology.

A stochastic simulation program of drug-receptor interaction is presented. The user can select a set of conditions concerning the processes of response release (type of cellular response, drug distribution and metabolism etc.) and the program plots a family of dose-response curves. A comparison between experimental and simulated dose-response curves shows the validity of the model can be used either for testing hypotheses concerning drug-receptor interaction, for experimental design or for estimation of some specific parameters. The program can also be used for educational purposes.

WEB-MO--a computer aided learning on WWW.

The paper presents an electronic textbook on World Wide Web (WWW), which present theoretical notions about the eyes' movements. It also contains clinical cases as example for the described notions. The application is being tested at the County Hospital, Department of Neurosurgery, Timisoara, Romania. The reaction of the educators and learners is quite positive. We think there will be a great learning tool for the future.

Classification criteria for simulation programs used in medical education.

Simulation programs are often used in medical education and their large variety allows a classification according to several criteria. A system of eight axes is proposed here for such a classification: topic area, system level, simulated feature, basic model, main purpose, results presentation, warnings, and evaluation.