Feasibility of health-related quality of life (HRQoL) assessment for cancer patients using electronic patient-reported outcome (ePRO) in daily clinical practice

Quality of Life Research - Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance...     

Wagner vitreoretinal degeneration with genetic linkage refinement on chromosome 5q13-q14

· Background: It has been previously described that Wagner disease is linked to chromosome 5q13-q14. This study was carried out to describe the ophthalmological aspects and report the results of genetic linkage analysis in a large pedigree affected by Wagner disease. · Methods: Fourty members of one same family agreed to be examined. · Results: Twenty patients presented vitreoretinal degeneration in both eyes without any extra-ocular abnormalities. In young patients, visual acuity was usually normal after correction of frequent mild myopia. Presenile cataracts progressed by the third decade and required removal for visual rehabilitation. The primary disorder involved an abnormal vitreous. A few avascular vitreous bands were usually the only optical feature in the mostly empty vitreous cavity. A circumferential vitreous condensation formed in contact with the retina on many spots. Less common retinal findings included retinal detachment, abnormal retinal pigmentation, progressive atrophy of the RPE simulating choroideremia and lattice degeneration. Genetic analysis revealed a highly significant linkage (lod score >5.0) between the disease and 10 markers of the chromosome 5q13-q14 region. Two recombination events allowed us to refine the linked interval to 20 cM between the D5S650 and D5S618 markers. · Conclusion: Ophthalmological aspects of Wagner’s disease appear to progress with age. Regular ophthalmological examination is important for detecting retinal abnormalities. The gene involved in Wagner’s disease lies in a 20 cM interval on chromosome 5q13-q14. Received: 30 June 1998 Revised version received: 5 October 1998 Accepted: 6 October 1998     

Prevalence and Clinical Significance of Her-2/neu, p53 and Rb Expression in Primary Superficial Bladder Cancer

Purpose

The usefulness of the expression of HER2/neu oncoprotein and of p53 and Rb suppressor gene product as predictors of tumor recurrence was evaluated by using a bank of prospectively collected primary papillary bladder tumors treated initially only by transurethral resection.

Materials and Methods

The expression of HER-2/neu oncoprotein and of p53 and Rb suppressor genes was evaluated by immunohistochemistry in 256, 265 and 74 specimens of primary Ta/T1 superficial bladder tumors obtained from patients enrolled in a prospective study from 1990 to 1992. Survival analysis was used to evaluate the association between time to first recurrence and expression of each marker, the follow-up period extending to March 1994. Immunostaining for p53 and HER-2/neu was performed on paraffin-embedded tissue and, for Rb, on frozen tissue only.

Results

Her-2/neu was expressed in 21 (8.2 percent) cases and p53 in 39 cases (14.7 percent); Rb expression was altered in 12 (16.2 percent). In this study, p53 expression was only related to earlier recurrence in a univariate analysis. Multivariate analysis, however, failed to recognize p53 expression as an independent predictor of recurrence.

Conclusions

Our study demonstrate the low prevalence of HER2/neu, p53 and altered Rb expression in superficial TCC at initial resection. Only p53 expression was significantly associated with an earlier first tumor recurrence, but this association was not independent of other prognostic factors.     

Comparative effects of L-methionine, S-adenosyl-L-methionine and 5'-methylthioadenosine on the growth of preneoplastic lesions and DNA methylation in rat liver during the early stages of hepatocarcinogenesis.

Male Wistar rats, initiated with diethylnitrosamine (DENA), were subjected to a selection treatment, according to the "resistant hepatocyte" model, followed or not followed by phenobarbital (PB). Rats received, for 3 weeks after selection, 4 i.m. doses (96 mmol/kg) of L-methionine, S-adenosyl-L-methionine (SAM), or 5'-methylthioadenosine (MTA), a SAM catabolite formed during polyamine synthesis or by spontaneous splitting of SAM at physiologic temperature and pH. They were then killed. In some rats, SAM and MTA treatments were started 20 weeks after initiation. The animals were killed 3 weeks later and persistent (neoplastic) nodules (PN) were collected. Some rat groups received 1/2 and 1/4 of the above SAM and MTA doses, or 1/8 of the above MTA dose. SAM and MTA, but not methionine, caused a dose-dependent decrease in number and surface area of gamma-glutamyltranspeptidase (GGT)-positive foci, and in labeling index (LI) of focal cells, coupled with remodeling. SAM and MTA liver contents, SAM/S-adenosylhomocysteine (SAH) ratio and overall methylation of liver DNA were low during the development of GGT-positive foci. SAM, but not methionine, caused a dose-dependent recovery of SAM content and DNA methylation, and a partial reconstitution of liver MTA pool. Exogenous MTA only induced the reconstitution of MTA pool, without affecting SAM level and DNA methylation. Recovery of SAM and MTA pool and DNA methylation was found in the rats subjected to SAM plus MTA, indicating the absence of inhibition of DNA methyltransferases in vivo by MTA. MTA also inhibited liver reparative growth in partially hepatectomized rats, without modifying SAM content and DNA methylation of regenerating liver (RL). A high activity of ornithine decarboxylase (ODC) was found in the liver, during the development of preneoplastic foci, and in PN. This activity was inhibited by SAM and MTA treatments. Although MTA was more effective than SAM, the decrease in ODC activity was coupled with a larger fall in DNA synthesis in SAM-treated than in MTA-treated rats. Thus the antipromotion effect of SAM could not merely depend on its (spontaneous) transformation into MTA. Although MTA production may play a role in the SAM antipromotion effect, other mechanisms could be involved. A role of DNA methylation in the inhibition of growth by SAM is suggested. MTA is a potential chemopreventive agent for liver carcinogenesis.     

Succinylcholine does not worsen bupivacaine-induced cardiotoxicity in pentobarbital-anaesthetized dogs

The intravascular injection of a large dose of bupivacaine induces electrophysiological cardiac impairment, mainly by slowing ventricular conduction velocity, and haemodynamic depression, by a decrease in myocardial contractility. When cardiotoxicity occurs, succinylcholine rapidly stops convulsions. However, the possible interactions between bupivacaine and succinylcholine on cardiac electrophysiology and haemodynamic status have never been investigated. Thus, we used an experimental electrophysiological model involving closed-chest dogs. Three groups (n = 6) of pentobarbital-anaesthetized dogs were given 0.2 mg.kg-1 atropine iv. Dogs in Group 1 were given saline. The others received 4 mg.kg-1 bupivacaine iv over ten seconds. Dogs in Group 2 were then given saline and those in Group 3 were then given 2 mg.kg-1 succinylcholine iv from one to two minutes after the administration of bupivacaine. The following electrophysiological variables were measured: heart rate represented by RR interval (RR), PR, atria-His (AH), and His-ventricle (HV) intervals, QRS duration, and QT interval corrected for heart rate (QTc). The following haemodynamic variables were measured: mean aortic pressure (MAoP), the peak of the first derivative of left ventricular pressure (LV dP/dt max), and LV end diastolic pressure (LVEDP). Comparison between Groups 1 and 2 showed that bupivacaine induced more than 100% HV interval lengthening and QRS widening (P less than 0.01), prolonged QTc interval by more than 25% (P less than 0.01), and decreased LV dP/dt max by more than 50% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Tissue oxygen tension and other indicators of blood loss or organ perfusion during graded hemorrhage

Currently employed clinical indicators of perfusion provide inadequate warning of developing hazards caused by marginal perfusion in certain vital organs or "peripheral" tissues that are pivotal to postsurgical wound healing. In this study, mean arterial blood pressure, cardiac output, and transcutaneous and subcutaneous oxygen tensions (PtcO2 and PsqO2) were investigated during serial hemorrhage, as indicators of the degree of both hypovolemia and perfusion to specific tissues. Blood was removed in stages (10%, 20%, 30%, 40%, 55%, 60%, and 65% of original volume) from anesthetized dogs. Injections of variously radiolabeled microspheres allowed assessment of blood flow at each stage of hemorrhage in bone, brain, colon, heart, kidney, liver, muscle, pancreas, skin, small intestine, spleen, stomach, and subcutaneous tissue. PsqO2 was correlated more highly with blood volume lost than was PtcO2. Furthermore PsqO2 was more sensitive to blood loss than was either cardiac output or PtcO2 and, also during the early loss (0% to 40%), was more sensitive than mean arterial pressure. Some organs (e.g., pancreas) appeared to lose considerable blood flow with only small loss of blood volume, but their blood flow then stabilized at a low level despite further hemorrhage. Other organs, notably the kidney, appeared to be relatively unaffected by substantial loss of blood volume (20% to 40%), after which, however, their blood flow quite abruptly became sensitive to further hypovolemia. This explains why blood flow-related performance of the kidney (e.g., urine volume) may not adequately predict a developing hazard or peripheral perfusion. Some indicators were found to be better indexes of blood flow in some organs than in others (e.g., cardiac output and PsqO2 correlated more closely with skin, spleen, and intestinal flows [and one another] than with vital organ flows).     

Clinical measurement, statistical analysis, and risk-benefit: controversies from trials of spinal injury

BACKGROUND: The National Acute Spinal Cord Injury Studies have been a series of trials assessing the role of pharmacologic agents in the prevention of secondary neuronal damage after acute spinal cord injury. METHODS: The trials were multicenter randomized, controlled studies. RESULTS: Two trials have demonstrated the efficacy of high-dose methylprednisolone in improving neurologic and functional recovery and have shown a reassuring safety profile. CONCLUSION: This study responds to a recent commentary on these trials and examines in particular the roles of clinical measurement, statistical analysis, and risk benefit in assembling evidence for or against innovative therapies.     

Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas.

PURPOSE: The reliability of immunohistochemistry for subdividing diffuse large B-cell lymphomas (DLBCL) into germinal center B-cell-like (GCB) and non-GCB prognostic subgroups is debated. In this study we evaluated the prognostic significance of such subgrouping on a series of 153 DLBCL patients. Furthermore, we investigated whether both subgroups could comprise clinicopathologic entities recognized by their morphology and characterized by a distinct phenotype, specific genetic abnormalities, and clinical characteristics. PATIENTS AND METHODS: All samples from patients were reviewed and morphologically subdivided into large cleaved, immunoblastic, and not otherwise specified DLBCL. GCB and non-GCB immunohistochemical profiles were established. The presence of chromosomal translocations involving BCL2, BCL6, and MYC and/or rearrangements of these genes was investigated. RESULTS: Subdividing DLBCL with either a GCB or non-GCB immunophenotypic profile was not of prognostic significance. Nevertheless, CD10 expression was a predictor of favorable outcome, whereas high bcl-2 expression and BCL6 rearrangement were adverse predictors of disease-free survival. Interestingly, large cleaved DLBCL was clearly associated with a GCB immunophenotypic profile, CD10 expression, BCL2 rearrangement, age younger than 60 years, and low to low/intermediate International Prognostic Index risk, but was not of prognostic significance. In contrast, immunoblastic morphology was associated with a non-GCB profile and was a significant predictor of unfavorable DFS. CONCLUSION: Subdividing DLBCL into subgroups based on their immunohistochemical profile was not of prognostic significance. Nevertheless, it allowed the additional characterization of two lymphoma subgroups previously recognized in the Working Formulation. Both correspond to two distinct clinicopathologic entities within the DLBCL.