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Importance of early ischemic computed tomography changes using ASPECTS in NINDS rtPA Stroke Study.

BACKGROUND AND PURPOSE: The importance of early ischemic change (EIC) on baseline computed tomography (CT) in the decision to thrombolyze the patient with acute ischemic stroke has been controversial. ASPECTS is a semiquantitative scale that scores the extent of EIC within the middle cerebral artery territory. We examined whether ASPECTS could be a treatment modifier by systematically reviewing the CT scans in the NINDS rtPA Stroke Study. METHODS: Six hundred eight of the 624 CT scans were available and of sufficient quality. One of 2 teams (n=3 each) of expert ASPECTS readers evaluated each scan for an ASPECTS value using a consensus score approach. Each team was blind to all clinical information except symptom side and blind to follow-up imaging and outcome information. ASPECTS values were stratified before analysis. Multivariable logistic regression was used to determine if an ASPECTS by treatment interaction existed on treatment response, outcome, and intracerebral hemorrhage risk. RESULTS: A total of 57.2% (348 of 608) of scans showed EIC with an ASPECTS <10. ASPECTS dichotomized into 8 to 10 and <8 did not have a treatment-modifying effect on good outcome but showed a trend to lower mortality at 90 days with tPA (relative risk 0.67, 95% confidence interval 0.41 to 1.06, P=0.10). ASPECTS 8 to 10 were associated with a trend to larger benefit of tPA with a number needed to treat (NNT) of 5 versus ASPECTS 3 to 7 with a NNT of 8. CONCLUSIONS: There was no evidence of treatment effect modification by the baseline ASPECTS value in the NINDS rtPA Stroke Study. Therefore, exclusion of patients for thrombolysis within 3 hours of symptom onset based on EIC is not supported by our data. There is a trend to reduced mortality and increased benefit to rtPA if the baseline CT scan is favorable (ASPECTS >7).

Aged↗

HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma.

BACKGROUND: The use of biologic markers to predict response to neoadjuvant chemotherapy may permit tailoring regimens to achieve maximal tumor response. Taxanes have demonstrated excellent activity in breast carcinoma; however, tumor-specific factors that predict clinical response have not been characterized thoroughly. METHODS: The authors performed a historic review evaluating the association of tumor prognostic factors and response to neoadjuvant cyclophosphamide and doxorubicin (AC) with or without docetaxel (D) (AC vs. AC+D) in 121 women who previously were enrolled in a Phase III, randomized, clinical trial. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53, and Ki-67. Outcome variables were pathologic complete response (pCR) and positive clinical response (cPOS), which was defined as a >/= 50% regression in clinical tumor size prior to surgery. RESULTS: In a multivariate analysis that controlled for tumor size and lymph node status, improved cPOS rates were observed with the addition of docetaxel in women with HER-2/neu-negative tumors (81% vs. 51%; P < 0.05), yielding an adjusted odds ratio of 3.5 (95% confidence interval, 1.2-13.0) in favor of docetaxel. Women who had HER-2/neu-negative tumors appeared to have a lower response rate with AC alone compared with women who had HER-2/neu-positive tumors (51% vs. 75%; P = 0.06), but response rates were matched when docetaxel was added (81% vs. 78%; P = 0.99). ER, PR, p53, and Ki-67 results were not associated significantly with response rates. CONCLUSIONS: HER-2/neu status may predict improved clinical response rates from the addition of docetaxel to anthracycline-based neoadjuvant chemotherapy. Docetaxel may "rescue" the response in women who have HER-2/neu-negative tumors to match that observed in women who have HER-2/neu-positive tumors treated with AC alone.

Adult↗

Composting of vegetable waste.

The effects of the aeration, seeding, and agitation on the composting of vegetable waste were studied in a laboratory-scale reactor. Experimental results showed that the final product at the end of a 4-day composting period met multiple maturity indices suggested by many researchers. The evolution of carbon dioxide during the composting process could be modelled with a modified Gompertz equation that described the bacteria growth successfully. Multivariate regression analysis was used to study the effects of operating parameters on the carbon conversion. The response surface contour plots were constructed using the regression equation for the examination of the dependence of carbon conversion on operating parameters. The maximum carbon conversion of 14.54% was obtained when the percentage of seeding was set at 14.5%, the air suction rate was set at 2.6 L kg(-1) dry-solid min(-1), and the agitator operated half of the time, alternating on and off for every 5 min. Future work will focus on the application of the data and the experience gained in this work to composters of pilot and semi-commercial scales.

Air↗

Comparison of physiological and radiological screening for lung volume reduction surgery.

Physiological and radiological criteria are both used to identify candidates for LVRS. This study compares the predictive value of these screening techniques among patients with homogeneous (Ho) and heterogeneous (He) emphysema. Preoperative inspiratory lung conductance (G(Li)) during spontaneous breathing and quantitative radioisotope V/Q scan (QVQS) results were available for 48 of 50 patients undergoing bilateral LVRS for emphysema. Ho disease (n = 21) was defined by QVQS as an upper/lower perfusion ratio (ULPR) between 0.75 and1.25. G(Li) correlated with 6-mo improvement in FEV(1) (DeltaFEV(1)-6) (r = 0.53, p < 0.001) for the entire cohort, and for patients with both Ho (n = 21, r = 0.56, p = 0.015) and He disease (n = 27, r = 0.46, p = 0.017). ULPR correlated less well with DeltaFEV(1)-6 (n = 48, r = -0.38; p = 0.008) for the cohort, and was significantly correlated with outcomes only in the subgroup of patients with He disease (r = -0.40, p = 0.04). Multivariate regression demonstrated that by combining G(Li) and ULPR criteria, 33% of the DeltaFEV(1)-6 response could be accounted for. We conclude that both physiological and radiological criteria help identify appropriate candidates for LVRS. G(Li) best identifies patients with Ho emphysema who may benefit from surgery, but would be excluded on the basis of strictly radiological criteria. ULPR helps identify patients with He disease that improves with surgery, despite unfavorable G(Li).

Adult↗

Predictive factors for beneficial response to interferon-alfa therapy in chronic hepatitis C.

OBJECTIVES: Interferon is the only established treatment for chronic hepatitis C but the host-dependent or virus-related factors affecting the response rate to interferon therapy are not yet clear. The purpose of this study was to investigate the factors predictive of response to interferon-alfa therapy in chronic hepatitis C. METHODS: Twenty-five consecutive patients with chronic hepatitis C were randomized to three regimens of interferon-alfa: group A (n = 7, 3 MU every day for 3 months), group B (n = 8, 3 MU every other day for 3 months) and group C (n = 10, 3 MU every other day for 6 months). We quantified serum HC RNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR) and performed HCV genotyping using type-specific primers deduced form the NS5 region of the HCV genome. We also attempted to identify which demographic, biochemical and histologic factors in addition to virus-related factors would significantly predict beneficial response to interferon by multivariate analysis. RESULTS: Sustained responders were 8 (36.4%), nonsustained responders were 2 (9.1%) and nonresponders were 12 (54.5%) of 22 patients who had received complete therapy. The initial HCV RNA level (logarithmic transformed copy numbers per ml of serum) in sustained responders (5.75 +/- 0.39) was significantly lower than that of nonsustained responders (6.80 +/- 0.71) and nonresponders (6.70 +/- 0.52) (p < 0.05). In multivariate multiple logistic regression analysis, the serum HCV RNA level before therapy was only the independent predictor of a sustained response to interferon-alfa therapy (p = 0.001). CONCLUSIONS: Serum HCV RNA level before therapy was the most useful predictor of a sustained response to interferon-alfa therapy for chronic hepatitis C.

Adult↗

Attitudes and perceptions toward hand hygiene among healthcare workers caring for critically ill neonates.

BACKGROUND: Infectious complications are frequent among critically ill neonates. Hand hygiene is the leading measure to prevent healthcare-associated infections, but poor compliance has been repeatedly documented, including in the neonatal setting. Hand hygiene promotion requires a complex approach that should consider personal factors affecting healthcare workers' attitudes. OBJECTIVE: To identify beliefs and perceptions associated with intention to comply with hand hygiene among neonatal healthcare workers. METHODS: An anonymous, self-administered questionnaire (74 items) based on the theory of planned behavior was distributed to 80 neonatal healthcare workers to assess intention to comply, attitude toward hand hygiene, behavioral and subjective norm perceptions, and perception of difficulty to comply. Variables were assessed using multi-item measures and answers to 7-point bipolar scales. All multi-item scales had satisfactory internal consistency (alpha > 0.7). Multivariate logistic regression identified independent perceptions or beliefs associated with a positive intention to comply. RESULTS: The response rate was 76% (61 of 80). Of the 49 nurses and 12 physicians responding, 75% believed that they could improve their compliance with hand hygiene. Intention to comply was associated with perceived control over the difficulty to perform hand hygiene (OR, 3.12; CI95, 1.12 to 8.70; P = .030) and a positive perception of how superiors valued hand hygiene (OR, 2.89; CI95, 1.08 to 7.77; P = .035). CONCLUSION: Our data highlight the importance of the opinions of superiors and a strong perceived controllability over the difficulty to perform hand hygiene as possible internal factors that may influence hand hygiene compliance.

Adult↗

Multivariate adaptive regression splines (MARS) in chromatographic quantitative structure-retention relationship studies.

The multivariate adaptive regression splines (MARS) methodology was applied to build quantitative structure-retention relationships (QSRRs). The response (dependent variable) in the MARS models consisted of the logarithms of the extrapolated retention factors (log k(w)) of 83 structurally diverse drugs on a Unisphere PBD column, using isocratic elutions at pH 11.7. A set of 266 molecular descriptors was used as predictor (independent) variables in the MARS model building. The optimal MARS model uses 34 basis functions to describe the retention and has acceptable predictive properties for new objects. The molecular descriptors included in the model describe hydrophobicity, molecular size, complexity, shape and polarisability. Some additional MARS models were created using alternative strategies. These include models with log P as the single predictor and models obtained with only the three most important molecular descriptors. The use of classification and regression trees (CART) as feature selection technique for predictor variables used in the MARS model was also investigated. Further, it is also studied whether allowing quadratic terms instead of interaction terms might lead to better MARS models.

Chromatography, Liquid↗

Acute service delivery in a police-mental health program for children exposed to violence and trauma.

The Child Development Community Policing Program represents a national model of community-based collaboration between police and mental health professionals for violence-exposed and traumatized children. Administrative data from clinical records of a 24-hour consultation service were examined through stepwise multivariate logistic regression to identify child and event characteristics associated with a direct, in-person response at the time of police contact. Of 2361 children, 809 (34.3%) received a direct, in-person response. Relative to Caucasian children, Hispanic youth were more likely to receive this form of response (OR = 1.36). An acute clinical response was more likely for incidents of gang involvement (OR = 8.12), accidents (OR = 5.21), felony assaults (OR = 2.97), property crimes (OR = 2.30), family violence (OR = 1.53) and psychiatric crises (OR = 1.29). Acute response was less likely when juvenile conduct problems (OR = 0.61), fires (OR = 0.59), child maltreatment (OR = 0.57), and domestic violence (OR = 0.44) were involved. Incidents that were more severe or involved a primary mental health component were related to utilization of intensive CDCP resources.

Adolescent↗

Daily consumption of (red) meat or meat products in Switzerland: results of the 1992/93 Swiss Health Survey.

OBJECTIVE: The present study aimed to examine the frequency of daily meat and meat product consumption and the preference for red meat in Switzerland. DESIGN: Cross-sectional Study. SETTINGS AND SUBJECTS: Data were taken from the 1992/1993 Swiss Health Survey, which collected data on a random sample of persons aged 15 and over, living in Switzerland. The survey, which had a response rate of 71%, included 7930 male and 7358 female respondents. Bivariate analyses and multivariate logistic regressions controlling for sociodemographic and lifestyle factors were performed. RESULTS: Daily consumption of meat or meat products (25%) and more frequent consumption of red than white meat (26% of meat eaters) were prevalent in Switzerland. Men, middle-aged persons, participants with a low level of education, persons living in the German or Francophone regions of Switzerland, those with Swiss nationality, smokers, overweight and obese people, those with daily alcohol consumption and physically inactive persons were found to consume daily meat or meat products more frequently. A preference for red meat rather than white meat was more often observed in men, young people, persons living in the German or Francophone regions of Switzerland, smokers and participants who consumed alcohol at least once daily. CONCLUSIONS: The analysis of data from the 1992/1993 Swiss Health Survey shows that in specific subgroups of the Swiss population meat and meat product consumption is still more frequent than recommended, but crude comparisons with older and more recent studies indicate a decrease in meat consumption. The observed clustering of daily meat consumption with other risk factors underscores the necessity to include dietary recommendations in health programs addressing other unhealthy lifestyles. European Journal of Clinical Nutrition (2000) 54, 136-142

Adolescent↗

Decompression surgery for lumbar spinal stenosis in the elderly: preoperative expectations and postoperative satisfaction.

STUDY DESIGN: Retrospective cohort examination. OBJECTIVES: Data on expectations and satisfaction rates in elderly patients operated for lumbar spinal stenosis (LSS) are limited. The present study aimed to investigate these issues as well as the factors that might affect them. SETTING: A university affiliated hospital. PATIENTS AND METHODS: A follow-up study of 367 consecutive patients aged 65 years and older (mean age 71.4 years), who underwent surgery for degenerative LSS between 1990 and 2000. Data collection included patients' preoperative expectation, demographic data, body mass index, operative risk, duration of symptoms, clinical presentation and patients' satisfaction on follow-up, pain level, activities of daily living level and walking ability. Data were recorded before operation and on follow-up. Preoperative and follow-up data were analyzed by univariate and multivariable models. RESULTS: The response rate on follow-up was 81% (298 patients). A logistic regression analysis showed that advanced age, male gender and high education level were independently associated with positive expectations, while a great number of covariates were associated with patients' satisfaction. High patients' expectations were positively interrelated with satisfaction (r=0.332, P<0.001). CONCLUSIONS: In the elderly, preoperative expectations reasonably predict their postoperative satisfaction rate. It is suggested that a greater effort should be made to narrow the gaps between expectations and satisfaction, perhaps by providing more accurate preoperative information data regarding the outcomes of planned surgery.

Activities of Daily Living↗

Pharmacogenetic characteristics of indinavir, zidovudine, and lamivudine therapy in HIV-infected adults: a pilot study.

OBJECTIVE: The aim of the study was to investigate relationships among indinavir, lamivudine-triphosphate, and zidovudine-triphosphate pharmacokinetics and pharmacodynamics with polymorphisms in CYP3A5, MDR1, MRP2, MRP4, BCRP, and UGT1A1 genes. STUDY DESIGN: Retrospective pilot investigation among 33 subjects who participated in a randomized pharmacological study of indinavir, lamivudine, and zidovudine. Subjects were defined as genetic variant carriers or not. Relationships were investigated with multivariable regression. Indinavir clearance was adjusted for African American race; triphosphates for sex; and HIV-response for study arm, drug exposure, and baseline HIV-RNA. RESULTS: Genetically determined CYP3A5 expressors had 44% faster indinavir oral clearance versus nonexpressors (P = 0.002). MRP2-24C/T variant carriers had 24% faster indinavir oral clearance (P = 0.05). Lamivudine-triphosphate concentrations were elevated 20% in MRP4 T4131G variant carriers (P = 0.004). A trend for elevated zidovudine-triphosphates was observed in MRP4 G3724A variant carriers (P = 0.06). The log10 changes in HIV-RNA from baseline to week 52 were -3.7 for MDR1 2677 TT, -3.2 for GT, and -2.2 for GG (P < 0.05). Bilirubin increases were 2-fold higher in UGT1A1 [TA]7/[TA]7 genotypes. No relationships were identified with BCRP. DISCUSSION: Novel relationships were identified among genetic variants in drug transporters and indinavir, lamivudine-triphosphate, and zidovudine-triphosphate concentrations. CYP3A5 expression was associated with faster indinavir oral clearance. These pilot data provide a scientific basis for more rational utilization of antiretroviral drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Quality of life, disability and handicap in patients with toxic oil syndrome.

AIM: This paper reports an investigation of the quality of life of patients most severely affected by toxic oil syndrome and the association between quality of life and disability variables, handicaps and depression. BACKGROUND: In 1981, an epidemic occurred in Central and Northwestern Spain. The illness, now called toxic oil syndrome (TOS), appeared to be caused by consumption of oil mixtures containing rapeseed oil denatured with aniline and affected over 20,000 individuals. Today, it is classified as a chronic disease that has resulted in a large number of sequelae. METHOD: From the 1031 people classified with permanent disability, a random sample of 292 individuals was selected. A structured interview was carried out to investigate the clinical aspects. The Nottingham Health Profile Questionnaire was used to assess quality of life. To study the relationship between quality of life and disability, handicap and depression, a univariate analysis was carried out. The chi-square test was used for inter-group comparisons. A P-value of 0.05 was adopted as the limit for inclusion of a variable in the multivariate analysis. Multivariate analysis was undertaken using logistic regression. RESULTS: Two hundred and fourteen patients were interviewed (79% response rate). Mean age was 59.3 (sd: 12.7) years. Quality of life mean score was 52.8 (sd: 22.6). The variables associated with poorer quality of life perception were depression [odds ratio (OR) = 9.66, confidence interval (CI) = 3.71-25.15], role-related disabilities (occupation role: OR = 2.82 CI = 1.28-6.22) and mobility (bending/picking up: OR = 4.74, CI = 2.31-9.72), as well as economic problems (OR = 1.62, CI = 1.07-2.46). CONCLUSION: The quality of life of those most severely affected by TOS is poor. Their health profile is characterized by depression and important functional and psycho-social disabilities that limit daily living activities and social roles, and are related to self-perceptions of poor quality of life.

Adult↗

Risk factors for shoulder and elbow injuries in adolescent baseball pitchers.

BACKGROUND: There is little evidence supporting current safety recommendations for adolescent pitchers. HYPOTHESIS: Pitching practices of adolescent pitchers without history of arm injury will be significantly different from those of adolescent pitchers who required shoulder or elbow surgery. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Ninety-five adolescent pitchers who had shoulder or elbow surgery and 45 adolescent pitchers who never had a significant pitching-related injury completed a survey. Responses were compared between the 2 groups using t tests and chi(2) analyses. Multivariable logistic regression models were developed to identify the risk factors. RESULTS: The injured group pitched significantly more months per year, games per year, innings per game, pitches per game, pitches per year, and warm-up pitches before a game. These pitchers were more frequently starting pitchers, pitched in more showcases, pitched with higher velocity, and pitched more often with arm pain and fatigue. They also used anti-inflammatory drugs and ice more frequently to prevent an injury. Although the groups were age matched, the injured group was taller and heavier. There were no significant differences regarding private pitching instruction, coach's chief concern, pitcher's self-rating, exercise programs, stretching practices, relieving frequency, pitch type frequency, or age at which pitch types were first thrown. CONCLUSION: Pitching practices were significantly different between the groups. The factors with the strongest associations with injury were overuse and fatigue. High pitch velocity and participation in showcases were also associated with increased risk for injury. CLINICAL RELEVANCE: New recommendations were made based on these results. Adherence to the recommendations may reduce the incidence of significant injury to adolescent pitchers.

Adolescent↗

Implementation and use of an electronic health record within the Indian Health Service.

OBJECTIVES: There are limited data regarding implementing electronic health records (EHR) in underserved settings. We evaluated the implementation of an EHR within the Indian Health Service (IHS), a federally funded health system for Native Americans. DESIGN: We surveyed 223 primary care clinicians practicing at 26 IHS health centers that implemented an EHR between 2003 and 2005. METHODS: The survey instrument assessed clinician attitudes regarding EHR implementation, current utilization of individual EHR functions, and attitudes regarding the use of information technology to improve quality of care in underserved settings. We fit a multivariable logistic regression model to identify correlates of increased utilization of the EHR. RESULTS: The overall response rate was 56%. Of responding clinicians, 66% felt that the EHR implementation process was positive. One-third (35%) believed that the EHR improved overall quality of care, with many (39%) feeling that it decreased the quality of the patient-doctor interaction. One-third of clinicians (34%) reported consistent use of electronic reminders, and self-report that EHRs improve quality was strongly associated with increased utilization of the EHR (odds ratio 3.03, 95% confidence interval 1.05-8.8). The majority (87%) of clinicians felt that information technology could potentially improve quality of care in rural and underserved settings through the use of tools such as online information sources, telemedicine programs, and electronic health records. CONCLUSIONS: Clinicians support the use of information technology to improve quality in underserved settings, but many felt that it was not currently fulfilling its potential in the IHS, potentially due to limited use of key functions within the EHR.

Attitude of Health Personnel↗

Physician concurrence with primary care guidelines for persons with HIV disease.

An anonymous questionnaire was mailed to 3 groups of physicians in British Columbia: 659 registrants of a province-wide human immunodeficiency virus (HIV) drug treatment programme (Group 1); 765 who had had a patient test positive for HIV (Group 2); and a random sample of 484 (Group 3). Questionnaires provided data about: physician's demographic and personal characteristics; HIV-related patient care experience; and 12 knowledge-based items. Responses were received from 65% of Group 1, 68% of Group 2 and 70% of Group 3, with complete information received from 38% of Group 1 and 50% of Groups 2 and 3. Summary knowledge scores were computed by comparing physician responses to recommendations of contemporary guidelines. Regression techniques identified associations between physician characteristics and knowledge scores. Multivariate analysis revealed an inverse relationship between knowledge and physician age in all groups (all P < 0.01). Increased knowledge was associated with the number of currently active HIV-positive patients in Groups 1 and 2 (all P < 0.001), and lack of specialization in Groups 2 and 3 (both P < 0.001).

Adult↗

The coagulative and cardiorespiratory responses to reamed intramedullary nailing of isolated fractures.

We measured the changes during operation in seven markers of coagulation in a prospective series of 84 patients with fractures of the tibia or femur who were undergoing reamed intramedullary nailing. All patients were also continually monitored using transoesophageal echocardiography to assess marrow embolism. In a subset of 40 patients, intraoperative cardiopulmonary function was monitored, using pulmonary and systemic arterial catheterisation. The procedure produced a significant increase in prothrombin time, activated partial thromboplastin time, the level of prothrombin fragments F1+2 and D-dimers, and a decrease in the fibrinogen level, suggesting activation of both the coagulation and fibrinolytic pathways. There was evidence of both platelet hyper-reactivity and depletion, as estimated by an increase in beta-thromboglobulin levels and a decrease in the platelet count. In the patients who had invasive monitoring there was an incremental increase in mean pulmonary arterial pressure, with the changes being greatest during insertion of the guide-wire and reaming. The change in markers of coagulation, pulmonary artery pressure and arterial oxygen partial pressures correlated with the intraoperative embolic response. Greater changes in these parameters were observed during stabilisation of pathological fractures and in those patients in whom surgery had been delayed for more than 48 hours. Seven patients with pathological fractures developed more severe hypoxic episodes during reaming, which were associated with significantly greater arterial hypoxaemia, a fall in the right ventricular ejection fraction and an increase in the mean pulmonary artery pressure, pulmonary capillary wedge pressure, central venous pressure and the pulmonary vascular resistance index. These changes suggested that the patients had transient intraoperative right heart strain. Eight patients developed significant postoperative respiratory compromise. They all had severe intraoperative embolic responses and, in the three who had invasive monitoring, there was a significantly greater increase in pulmonary artery pressure and alveolar-arterial oxygen gradient, and a fall in the ratio of arterial partial pressure of oxygen to the inspired oxygen concentration. Operative delay, intraoperative paradoxical embolisation and the scores for the severity of the coagulative and embolic responses were predictive of the development of postoperative respiratory complications on univariate logistic regression analysis. On multivariate analysis, however, only the embolic and coagulative scores were significant independent predictors of respiratory complications.

Cardiovascular Diseases↗

Expression of p21 and MDM-2 proteins on tumor cells in responding and non-responding patients with Hodgkin's disease.

Since the prevention of apoptosis can produce resistance to chemotherapy, abnormal expression of oncoproteins engaged in the regulation of this phenomenon in tumor cells may give some prognostic information in patients with neoplasma. To assess this problem in Hodgkin's disease (HD), the cellular expression of two p53 downstreams proteins p21 and MDM-2 was evaluated in the lymph nodes specimens obtained from 68 patients at the time of diagnosis, and compared with some clinical and pathological data. Positive immunoreaction for p21 and MDM-2 on Reed-Sternberg/Hodgkin's (R-S/H) cells was found in a majority of cases (58.8 and 63.2%, respectively). High expression of p21 protein correlated with poor response to the first-line treatment and disease free survival in both univariate and multivariate regression analysis, whereas expression of MDM-2 did not give prognostic information in patients with HD. Expression of p21 and MDM-2 was also compared with p53 protein immunoreactivity of R-S/H cells. The p21+/p53+ immunophenotype occurred to give particularly negative prognostic information in patients with HD. Diversity of p21/MDM-2/p53 patterns of R-S/H cells observed in particular patients may reflect heterogeneity of apoptosis regulatory mechanisms, as well as differences in p53 gene status.

Adolescent↗

[Left ventricular filling studied by echo-Doppler in hypertensive and normotensive subjects].

Purpose of the study was to evaluate the influence of different clinical and echocardiographic parameters on left ventricular diastolic filling in a group of 66 mild to moderate hypertensive subjects (mean age = 45.9 +/- 13.9 yrs) and in 49 normotensive controls (mean age = 44.2 +/- 15.9 yrs). All subjects underwent an echocardiographic study with pulsed Doppler evaluation of left ventricular filling. In the hypertensives, a noninvasive 24-hour blood pressure monitoring was performed. The ratio of early to atrial peak diastolic filling velocity (VmaxE/VmaxA) and the ratio between the respective velocity flow integral (Earea/Aarea) were significantly lower in the hypertensives compared to the normotensives (p less than 0.001). As within the hypertensives, office systolic blood pressure, average 24-hour mean blood pressure (24MBP), left atrial dimensions, and left ventricular mass index (MAXIND) were related both to age and diastolic filling. To study the relation between these parameters and diastolic filling a partial correlation test was used. The only variable related to diastolic filling, independently of age, was 24MBP (VmaxE/VmaxA vs 24MBP: r = -0.307, p less than 0.05, Earea/Aarea vs 24MBP: r = -0.261, p less than 0.05). Linear multivariate analysis using the method of stepwise regression established that age, 24MBP and heart rate were responsible for 75% of the VmaxE/VmaxA variance in the hypertensive group. To evaluate if the difference between the indexes of diastolic filling in the normotensives and the hypertensives varied according to age, we divided each group into two classes of subjects older and younger than 40 yrs. Under the age of 40 only VmaxE/VmaxA was significantly different in the two groups (p less than 0.05), while in the subjects older than 40 yrs both VmaxE/VmaxA and Earea/Aarea differed to a great level of statistical significance (p less than 0.001). The results of the present study allow the following conclusions: 1) age has the greatest influence on diastolic filling in both hypertensive and normotensive individuals. Diastolic filling is impaired in mild to moderate hypertension, when systolic function is still normal; 2) the worsening of diastolic filling determined by hypertension is more evident in the subjects greater than 40 yrs; 3) the only clinical variable that influences diastolic filling, independently of age, is 24MBP, while office blood pressure, MAXIND and left ventricular ejection fraction do not seem to be related to this clinical entity.

Adolescent↗