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D Collins

Publications and source records attributed to D Collins.

At least 127 records · Page 7Linked to original sources
PubMed1988

Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma.

Von Hippel-Lindau disease (VHL) is an autosomal dominant disorder with inherited susceptibility to various forms of cancer, including hemangioblastomas of the central nervous system, phaeochromocytomas, pancreatic malignancies, and renal cell carcinomas. Renal cell carcinomas constitute a particularly frequent cause of death in this disorder, occurring as bilateral and multifocal tumours, and presenting at an earlier age than in sporadic, non-familial cases of this tumour type. We report here that the VHL gene is linked to the locus encoding the human homologoue of the RAF1 oncogene, which maps to chromosome 3p25 (ref. 4). Crossovers with the VHL locus suggest that the defect responsible for the VHL phenotype is not a mutation in the RAF1 gene itself. An alternative or prior event to oncogene activation in tumour formation may be the inactivation of a putative 'tumour suppressor' which can be associated with both the inherited and sporadic forms of the cancer. Sporadic renal cell carcinomas have previously been associated with the loss of regions on chromosome 3p (refs 5, 6). Consequently, sporadic and VHL-associated forms of renal cell carcinoma might both result from alterations causing loss of function of the same 'tumour suppressor' gene on this chromosome.

Angiomatosis↗
PubMed1987

Esthesioneuroblastoma masquerading as extramedullary plasmacytoma.

Nine years after biopsy and radiation therapy for an extramedullary plasmacytoma of the nasal cavity, a 64-year-old man developed locally recurrent tumor. Repeat biopsy revealed tumor identical in hematoxylin and eosin stain (H & E) appearance to that found originally, leading to the diagnosis of recurrent extramedullary plasmacytoma. Neither the original tumor or its recurrence demonstrated features characteristic of esthesioneuroblastoma (e.g., nests, rosettes, ganglion cells, or fibrillary background). However, Gremilus staining and neuron specific enolase tests (immunoperoxidase method), done strictly as a teaching exercise, were strongly positive and eventually resulted in an altered diagnosis to esthesioneuroblastoma. This case underscores the difficulty that may be encountered in distinguishing these two pathologic entities of the nasal cavity solely on the basis of H & E staining. In view of differences in staging, evaluation, prognosis, and management, accurate differentiation of these two relatively uncommon tumors of the nasal cavity is of immediate clinical importance. These observations suggest that care should be taken to exclude the possibility of esthesioneuroblastoma before making the histologic diagnosis of extramedullary plasmacytoma of the nasal cavity.

Diagnosis, Differential↗
PubMed1987

Cytotoxicity of diphtheria toxin A fragment to toxin-resistant murine cells delivered by pH-sensitive immunoliposomes.

pH-sensitive immunoliposomes composed of dioleoylphosphatidylethanolamine and oleic acid (8:2 molar ratio) mediated the delivery of the cytotoxic fragment A of diphtheria toxin to the cytoplasm of target L-929 cells. Free fragment A, fragment A encapsulated in antibody-free liposomes, or fragment A encapsulated in pH-insensitive immunoliposomes was not effective in the inhibition of the cellular protein synthesis. pH-sensitive immunoliposomes containing diphtheria fragment A were not toxic to nontarget diphtheria-resistant A31 cells or to nontarget diphtheria-sensitive Vero cells. Pretreatment of target L-929 cells with the weak bases NH4Cl or chloroquine, agents which raise the endosome/lysosome pH, blocked the cytotoxic effect of the pH-sensitive immunoliposomes containing fragment A. Excess free antibody or excess empty pH-sensitive immunoliposomes also blocked the cytotoxic effect. Since it is known that fragment A alone cannot cross lipid membranes, the results of this study indicate that pH-sensitive immunoliposomes are able to release the toxin into the cytoplasm, probably by fusing with the endosome membrane following a receptor-mediated endocytosis of the immunoliposome.

Animals↗
PubMed1987

Nasopharyngeal carcinoma, aplastic anemia, and various malignancies in a family: possible role of Epstein-Barr virus.

We report on a family ascertained because of sibs affected with nasopharyngeal carcinoma. Other relatives had aplastic anemia or other malignancies and most were born of consanguineous parents. Epstein-Barr virus has been strongly implicated in the pathogenesis of nasopharyngeal carcinoma. It has also been suggested as a cause of aplastic anemia and other neoplasms. We postulate that this extensive German-Mennonite family has a heritable defect in the immune response to Epstein-Barr virus making its members at excessive risk for a number of different malignancies. This immunologic predisposition may be HLA associated and appears to be inherited as an autosomal recessive trait.

Adolescent↗
PubMed1987

Proximal 3p deletion in renal cell carcinoma cells from a patient with von Hippel-Lindau disease.

A case of proximal 3p deletion is reported in tumor cells from a patient with renal cell carcinoma and von Hippel-Lindau disease. This is the first report of this deletion with renal cell carcinoma. With the previously detected translocations at the same breakpoint, this report confirms the 3p14 breakpoint as critical in this neoplasm. This strongly suggests that renal cell carcinoma results from a change in the genetic material in the proximal short arm of chromosome #3.

Angiomatosis↗
PubMed1987

Plasma intestinal alkaline phosphatase and intermediate molecular mass gamma glutamyltransferase activities in the differential diagnosis of jaundice.

An assessment was made of the value of: (i) the demonstration of intestinal alkaline phosphatase in plasma for the differentiation of intrahepatic from post-hepatic jaundice in 122 jaundiced patients; and (ii) the demonstration of an intermediate molecular mass gamma glutamyltransferase in plasma for the identification of post-hepatic cholestasis in 74 jaundiced patients. The first test had a diagnostic sensitivity of only 32% with a specificity of 86%; the second test had a sensitivity of 50% and specificity of 75%. It is concluded that neither procedure is worth while.

Alkaline Phosphatase↗
PubMed1986

Limitations and advantages of the ejection fraction for defining high risk after acute myocardial infarction.

Left ventricular (LV) ejection fraction (EF) is known to be related to prognosis after acute myocardial infarction (AMI), but its role alone and in combination with other factors in the definition of a high-risk group has not been adequately specified. Several recent multicenter studies emphasize that LVEF together with features of ventricular ectopic activity during ambulatory electrocardiography define a group at high risk for death for up to 3 years. However, these high-risk groups comprised only a small fraction of the population (less than 7.5%) and failed to include 75% or more (less than 25% specificity) of observed events. In our study, LVEF was determined close to the time of hospital discharge in 750 patients with AMI enrolled in a collaborative study. Used alone, an LVEF of less than 0.45 best defined a high-risk group (39% of the population) yielding 62% sensitivity and 64% specificity for total cardiac mortality by 1 year; it was 77% sensitive for sudden death alone. In a multivariate analysis together with other factors, LVEF was an independent predictor, but other markers of LV dysfunction entered before LVEF with similar sensitivity for total cardiac deaths, but with increased specificity (75%). When an LVEF of less than 0.45 was used together with the presence of complex arrhythmias to define a high-risk group (19% of the population), sensitivity decreased to 39% and specificity increased to 84%. Thus, LVEF is a simple and effective alternative to multivariate analysis for risk assessment after AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Complexes, Premature↗
PubMed1986

The murmur of papillary muscle dysfunction in acute myocardial infarction: clinical features and prognostic implications.

The systolic murmur of papillary muscle dysfunction is a well-recognized feature of acute myocardial infarction (AMI), but no large prospective studies have determined its incidence, associated variables, and prognostic implications. Of 1653 patients who entered our data base with MI, 283 (17%) were classified as having a systolic murmur suggesting mitral regurgitation. At hospital discharge, there was a 5% incidence. There was a higher incidence of systolic murmur in non-Q wave AMI than in inferior or anterior Q wave MI (24% vs 13% and 15%, p less than 0.001). Advanced age, previous MI, and heart failure were all associated with systolic murmur (p less than 0.01). Persistent pain in the coronary care unit occurred more often in those with systolic murmur (45% vs 26%, p less than 0.0001). Systolic murmur was associated with an S3 and bibasilar rales (p less than 0.001) in the hospital; however, it was inversely related to peak creatine kinase and unrelated to heart failure or ejection fraction at discharge. Univariate predictors of mortality associated with systolic murmur included complex premature ventricular contractions at discharge and a non-Q wave location. Patients with systolic murmur had higher hospital and 1-year mortalities than those without systolic murmurs (p less than 0.01). When systolic murmur was present during hospitalization, the average time to reinfarction was 2.5 times earlier than when no systolic murmur was present (84 vs 214 days, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Technetium-99m-pyrophosphate scintigraphy in patients with suspected acute myocardial infarction: impact of interobserver variability.

Technetium-99m-pyrophosphate (TcPYP) scintigraphy may have great value in patients with suspected acute myocardial infarction (AMI), but interobserver variability undoubtedly has adverse impact on predictive value. TcPYP scintigrams for 133 (80%) of 166 consecutive patients admitted for suspected AMI were interpreted independently by three experienced readers. Although there was complete agreement for 87 interpretations (65%), major discrepancies (i.e., at least one positive and one negative reading on the same scan) occurred for 28 scans (21%). To assess predictive accuracy, patients were categorized as follows: 36 had definite AMI manifest by new ECG Q waves and/or CK-MB evidence of AMI (group I), 56 were classified as possible AMI (group II), and 41 had AMI excluded (group III). Using only the definitive diagnostic categories (groups I and III), accuracy for each reader approximated 0.68, with no single reader being correct more often than any other.

Creatine Kinase↗
PubMed1985

Survival after hospital discharge in matched populations with inferior or anterior myocardial infarction.

Prognostic differences between patients with anterior or inferior myocardial infarction are often related to such variables as previous infarction or the size of the myocardial infarct. We examined the determinants of mortality in 997 hospital survivors of acute Q wave infarction (anterior in 449, inferior in 548) who, although not preselected, were well matched with respect to age, sex and prior infarction or congestive heart failure. Additionally, there was no significant difference in peak serum creatine kinase (CK) between the groups with anterior and inferior infarction (1,459 +/- 1,004 versus 1,357 +/- 1,036). Among the patients with anterior infarction who died during the 1 year follow-up period, 56% died in the first 60 days after hospital discharge compared with 18% of those without inferior infarction (p less than 0.01). Survival curves then became nearly identical at 3 months, and remained so until 1 year when the total mortality rate was 10% for the anterior and 7% for the inferior infarction group (p = NS). Variables associated with heart failure during the hospital phase were more prevalent in anterior infarction, but rales above the scapulae during the hospital stay (p less than 0.0001) and ventricular gallop at the time of discharge (p less than 0.0001) were the top two predictors of 1 year mortality by both univariate and multivariate analysis in inferior infarction. Age (p less than 0.0001) and peripheral edema (p less than 0.0001) were the strongest predictors of mortality in anterior infarction. Previous infarction, although just as common in the group with anterior infarction, was present at 1 year in 48% of nonsurvivors of the group with inferior infarction compared with only 19% of survivors (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Prognosis after extension of myocardial infarct: the role of Q wave or non-Q wave infarction.

We examined whether or not subsets of patients with extension of myocardial infarct were at high risk for early and late mortality. Some data suggest increased risk in patients with non-Q wave infarcts and we hypothesized that infarct extension in this group might be associated with a poorer prognosis than that for patients with extension of Q wave infarcts. A total of 1253 patients with acute myocardial infarction who were included in our data base were followed prospectively. The patients were classified according to electrocardiographic results into the following groups: those with non-Q wave (n = 277) infarcts and those with Q-anterior (n = 462) and Q-inferior (n = 497) infarcts. Extension was diagnosed by two of the following criteria: (1) recurrent chest pain 24 hr or more after admission to the hospital, (2) new persistent electrocardiographic changes, and (3) elevation or reappearance of creatine kinase. By these criteria 85 (6%) patients had extension (8% of non-Q wave infarcts, 6% of Q-anterior infarcts, and 6% of Q-inferior infarcts). Hospital mortality in patients with extension was 15% in those with Q wave infarcts vs 43% in those with non-Q wave infarcts (p less than .01). Nine hundred and fifty-two patients were followed for 1 year. In 24% of those who did not survive 1 year there was extension of infarct; only 6% of survivors had extension (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

Complex ventricular arrhythmias in patients with Q wave versus non-Q wave myocardial infarction.

We examined whether or not subsets of patients with complex ventricular arrhythmias after myocardial infarction are at high risk with respect to 1 year mortality after hospital discharge. Based on previous studies showing increased risk for those with non-Q wave infarcts, we hypothesized that complex PVCs (premature ventricular complexes) in this group might be associated with a poorer prognosis than complex PVCs in patients with Q wave infarcts. Seven hundred seventy-seven patients entering our study with acute infarction were followed prospectively for 1 year after undergoing a predischarge 24 hr ambulatory electrocardiographic examination. Patients were classified by electrocardiographic criteria into the following groups: Non-Q wave (n = 191), Q wave anterior (n = 261), and Q wave inferior infarction (n = 325). The following arrhythmias were classified as complex: multiform PVCs, couplets, and ventricular tachycardia. Sixty-two percent of patients with non-Q wave infarcts who did not survive 1 year had complex PVCs, compared with 32% of survivors (p less than .01). No differences were seen in the Q wave subgroup. The survival for patients with Q wave and non-Q wave infarction without complex PVCs were nearly identical at 1 year (93% and 90%), whereas in patients with complex PVCs survival for those with Q wave and non-Q wave infarction was 92% and 76%, respectively (p less than .001). Of those with non-Q wave infarction, only 4% of nonsurvivors were free of any PVCs, as compared with 28% of nonsurvivors in the Q wave group (p less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

Prediction of late mortality after myocardial infarction from variables measured at different times during hospitalization.

The long-term prognostic importance of sets of variables from different times in the hospital course after acute myocardial infarction was examined in 818 patients discharged from the hospital. Cardiac mortality during the first year after discharge was 11.1%. For the end point death within 1 year after admission, discriminant function analysis identified 5 important factors from the history and the first 24 hours of hospitalization: maximal level of blood urea nitrogen, previous myocardial infarction, age, displaced left ventricular apex (abnormal apex) on physical examination, and sinus bradycardia (negative correlation). When data from the entire hospitalization were included, extension of infarction and maximal heart rate were also selected. When variables obtained at discharge were included, only the presence of S3 gallop and abnormal apex were selected. In subgroups of patients, neither the left ventricular ejection fraction nor the presence of complex ventricular arrhythmias during a 24-hour ambulatory monitoring were independent predictors. Correct prediction was similar for each analysis, with 55 to 60% of the deaths and 79 to 81% of survivors correctly identified. The high-risk group consisted of 25% of the patients with 28 to 30% predictive value for death in the first year. In conclusion, outcome up to 1 year after acute myocardial infarction can be predicted early after admission. Addition of more information later during the hospitalization and at discharge did not improve correct prediction and may be redundant for prognostic evaluation.

Aged↗
PubMed1984

Prognostic importance of digitalis after acute myocardial infarction.

Because previous reports have suggested that digitalis administration may lead to increased mortality after hospital discharge for acute myocardial infarction, the independent importance of digitalis therapy in long-term prognosis after acute myocardial infarction was investigated by analyzing 1,599 patients after definite myocardial infarction. After hospital discharge, mortality rate for the entire group at 4 months was 7.7% and after 1 year 14.2%. At discharge, 36.6% of the patients were taking digitalis. Compared with those not taking digitalis, those taking digitalis had more historical risk factors and a higher incidence of important clinical prognostic variables during the hospitalization. Their cardiac mortality rate after 4 months and 1 year (12.5 and 22.4%, respectively) was significantly higher than that of patients not taking digitalis (5.0 and 9.6%, respectively). Mortality was higher for patients taking digitalis whether or not they had congestive heart failure during hospitalization. However, in a multivariate Cox analysis for 1 year outcome, neither digitalis nor any other medication variable displaced the important clinical variables of age, congestive heart failure during the hospitalization, previous myocardial infarction, maximal heart rate during the hospitalization and previous angina. Quinidine and digitalis at discharge were selected sixth and seventh (not significant) by the analysis. It is concluded that digitalis therapy at discharge after myocardial infarction was not an independent predictor of late mortality in these patients.

Aged↗