Fatty acids and progression of coronary artery disease.
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Analysis of Variance↗
Biomedical subjects
R Morgan
Publications and source records attributed to R Morgan.
Counselling implications of chromosomal abnormalities other than trisomy 21 detected through a maternal serum screening programme.
OBJECTIVE: To identify counselling requirements, we reviewed the frequency and type of non-trisomy 21 chromosome abnormalities found at amniocentesis after maternal serum screening for Down's syndrome. DESIGN: The study involved a review of the cytogenetic results of amniocenteses performed because of a raised maternal serum screening risk. SETTING: The maternal serum screening and amniocenteses were performed at hospitals in the Yorkshire region. SAMPLE: 1715 amniocenteses were performed as a result of a raised maternal serum screening risk for the period 1990 to 1993. METHODS: The cytogenetic results were classified into the main categories of numerical and structural chromosomal abnormalities. MAIN OUTCOME MEASURES: The nature and frequency of abnormal cytogenetic results were identified in which parental samples were required in order to determine if the abnormal finding was de novo or familial and/or for which specialist genetic counselling was required. RESULTS: Sixty-nine pregnancies of 1715 amniocenteses were identified with a chromosomal abnormality (4.0%): 35 (2.0%) with trisomy 21 and 34 (2.0%) with another chromosomal abnormality. For 20 of these 34 abnormalities, parental karyotypes were required and in 29 of the 34 specialist genetic counselling was required. CONCLUSIONS: Women undergoing maternal serum screening and, in particular, those proceeding to amniocentesis, should be informed that there is an equal chance that a chromosomal abnormality other than trisomy 21 will be found at amniocentesis, the nature of which usually requires parental samples and specialist counselling.
Amniocentesis↗
High-dose chemotherapy and stem-cell rescue in the treatment of high-risk breast cancer: prognostic indicators of progression-free and overall survival.
PURPOSE: To examine the predictive value of tumor- and treatment-specific prognostic indicators of relapse-free survival (RFS) and overall survival (OS) in patients with high-risk breast cancer (HRBC) treated with high-dose chemotherapy (HDCT) and stem-cell rescue. PATIENTS AND METHODS: Between June 1989 and September 1994, 114 patients with HRBC (stage II with > or = 10 axillary lymph nodes involved, stage IIIA, and stage IIIB inflammatory carcinoma) received adjuvant chemotherapy followed by HDCT with etoposide, cyclophosphamide, and either doxorubicin (CAVP) or cisplatin (CCVP). Variables analyzed included stage, tumor size, number of axillary nodes involved, grade and receptor status, and types of adjuvant chemotherapy and radiation therapy and HDCT. RESULTS: With a median follow-up time of 46 months (range, 23 to 93), Kaplan-Meier estimates of 3.5-year OS for stage II, IIIA, and IIIB HRBC are 82% (95% confidence interval [CI], 67% to 97%), 79% (95% CI, 67% to 91%), and 72% (95% CI, 53% to 91%); RFS estimates are 71% (95% CI, 56% to 85%), 57% (95% CI, 43% to 72%), and 50% (95% CI, 29% to 71%) irrespective of the HDCT regimen. In univariate analysis, the risk of relapse was lower for patients with progesterone receptor (PR)-positive tumors (risk ratio [RR], 0.43; 95% CI, 0.22 to 0.81; P = .01) and higher for patients with inflammatory carcinoma (RR, 2.20; 95% CI, 1.02 to 4.76; P = .05). OS was better for patients with PR (RR, 0.16; 95% CI, 0.05 to 0.55; P = .003) and estrogen receptor (ER)-positive tumors (RR, 0.42; 95% CI, 0.17 to 1.02; P = .05); OS was worse for patients with high-grade primary tumors (RR, 4.08; 95% CI, 1.21-13.7; P = .02). In multivariate analysis, PR positivity was associated with improved RFS (P = .01) and OS (P = .001). CONCLUSION: HDCT in selected patients with HRBC is safe and warrants further evaluation. Patients with receptor-negative, high-grade, or inflammatory tumors require improvement in their therapeutic options. Better assessment of the role of HDCT awaits completion of ongoing randomized trials.
Adult↗
The role in neural patterning of translation initiation factor eIF4AII; induction of neural fold genes.
Expression of the RNA-helicase translation initiation factor, eIF4AII, in animal cap explants of Xenopus specifically upregulates genes expressed early in the neural plate border such as Xsna, Xslu, Pax-3 and XANF and also the cement gland marker XCG-1. eIF4AII is expressed specifically in the prospective neurectoderm from stage 11.5 and appears to have a significant role in mediating early patterning of the neurectoderm. It is induced by all known neural inducing regimes including secreted factors such as noggin, follistatin and chordin, transcription factors such as XlPou-2 and constructs that overcome repression of neural induction (tBMP-4R, lim-m3 and Xbra delta 304). It is also upregulated when neurulization occurs in embryonic ectoderm that has been disaggregated and reaggregated. While high amounts of injected mRNA of the neural inducers noggin, tBMP-4R and Xlpou-2 downregulate Xslu and upregulate the neural plate NCAM, smaller amounts of these mRNAs activate expression of eIF4AII and Xslu and suppress expression of epidermal keratin in animal cap assays. Ectopic expression of eIF4AII mRNA also upregulates transcription of the PKC alpha and beta genes. The sensitivity of the upregulation of neurectodermal markers to GF109203X indicates that the activity of a calcium activated protein kinase C (PKC) is also required. Furthermore ectopic expression of mouse eIF4AII mRNA upregulates the endogenous eIF4AII gene by a process that requires the activity of PKC. The effects of eIF4AII appear to be direct as conditional expression of eIF4AII in animal cap explants at the equivalent of stage 11.5 induces the endogenous eIF4AII and neural fold genes within 40 minutes. Expression of eIF4AII and activation of PKC sensitizes the embryonic ectoderm to the neuralising effect of noggin. We suggest that in developing embryos the neuralizing signal emanating from the organiser at first induces eIF4AII and the prospective neural crest in an arc low on the dorsal aspect of the embryo. As the neuralizing signal increases in intensity close to the organizer region, the tissue becomes committed to a neural plate phenotype. Expression of Xash-3A may suppress further expression of neural plate border genes within the prospective neural plate thereby subdividing the neurectoderm into two distinct regions.
Animals↗
The role of metallic stents in malignant duodenal obstruction.
Malignant duodenal obstruction is a common complication of carcinoma of the head of the pancreas. We report successful palliative treatment of malignant duodenal strictures by the peroral placement of metallic endoprostheses in two patients in whom palliative surgery was not possible.
Aged↗
Using uncovered metallic endoprostheses to treat recurrent benign esophageal strictures.
OBJECTIVE: The management of recurrent benign esophageal strictures is a difficult clinical problem, especially in patients who are not surgical candidates. We evaluated the role of uncovered metallic endoprostheses in four patients who had strictures that were resistant to repeated balloon dilatation. CONCLUSION: Our preliminary experience indicates that uncovered metallic endoprostheses can be effective in treating a select group of patients who have benign esophageal strictures and for whom multiple dilatations have failed. It is also important to note that epithelial hyperplasia can result in stenoses and recurrent dysphagia.
Aged↗
Surgical management of anorectal incontinence due to internal anal sphincter deficiency.
BACKGROUND: The aetiology, surgical management and outcome in 15 patients with anorectal incontinence due to internal and sphincter (IAS) deficiency as a result of previous anal surgery (n = 14) or penetrating trauma (n = 1) was studied. METHODS: The degree of anorectal incontinence was scored by the Cleveland Clinic system; median score was 14 (range 11-16) before surgery. In all patients the anal sphincter mechanism was assessed by endoanal ultrasonography. Thirteen of the 15 patients underwent either rotation (n = 5), island (n = 5) or advancement (n = 3) anoplasty to correct the contour defect in the anal canal. In the remaining two patients direct IAS repair was performed. RESULTS: Four of the 13 patients who underwent anoplasty developed wound breakdown as the result of infection (n = 3) or inadvertent suture removal (n = 1). A defunctioning stoma was required in three of these patients but all of these have been closed. At median follow-up of 34 (range 6-72) months, all patients who underwent anoplasty have normal defaecatory control and a median continence score of 2 (range 0-4). Direct IAS repair produced no symptomatic improvement in either patient. CONCLUSION: These results suggest that anoplasty deserves further evaluation in the treatment of anorectal incontinence due to discrete IAS defects, but that the place of IAS repair remains uncertain.
Adult↗
Anatomy of an earmold: a formal terminology.
The science of earmold (or hearing aid shell) modification has achieved a level that exceeds existing terminology. To date, there is no standardized terminology for various areas of the earmold and hearing aid shell. This article outlines a system of terminology that conforms with anatomic naming principles, retains current terminology where appropriate, and provides nomenclature for previously unnamed areas. A formal nomenclature should aid teaching and communication among professionals.
Ear, External↗
Older people's perceptions about symptoms.
BACKGROUND: Little is known of the nature and origins of the attitudes that older people have towards ageing, disease, and medical treatments. Several studies on older people in the community have suggested under-reporting of symptoms. There may be several reasons for this, including the possibility that some older people regard disease processes as a natural feature of ageing and, consequently, feel that medical intervention may have little to offer. AIM: To investigate the perceptions of older people about the significance of symptoms and what action they would take in response to particular symptoms. METHOD: Thirty-three men and 77 women attending social clubs (median age 78 years) were opportunistically selected and assessed using a supervised questionnaire. RESULTS: Many symptoms classically associated with common diseases were often considered to represent disease as well as to be normal for old people. Most would consult a doctor if they were to experience them. Some important symptoms, such as blackouts or paralysis of a limb, were not considered to be normal. Non-specific symptoms of psychiatric disturbances were also frequently considered normal but were not considered to represent disease. Whether or not a doctor would be consulted was often, but not always, related to whether a symptom was thought to represent a disease. Consulting a pharmacist was seldom considered appropriate. CONCLUSIONS: Doctors working with elderly people need to consider how beliefs about health and disease might affect what is reported to them. Specific enquiry needs to be made about symptoms of psychiatric disturbances. These findings suggest that there is a case for increased health education at retirement age.
Aged↗
BCL3 rearrangements and t(14;19) in chronic lymphocytic leukemia and other B-cell malignancies: a molecular and cytogenetic study.
The t(14;19)(q32.3;q13.1) is a recurring translocation found in the neoplastic cells of some patients with chronic lymphocytic leukemia (CLL) or other B-lymphocytic neoplasms. We previously cloned the translocation breakpoint junctions present in the leukemic cells from three such patients and identified a gene, BCL3, whose transcription is increased as a result of the translocation. In the present paper, we describe three additional patients with the t(14;19), one with lymphoma and two with CLL, and report the cloning and sequencing of the breakpoint junction in one of these patients as well as in a previously reported patient. We and others have found that the breakpoints on chromosome 14, with one exception, fall within the switch region upstream of the immunoglobulin heavy chain C alpha 1 or C alpha 2 sequences. Several of the breaks within chromosome 19 fall immediately upstream of the BCL3 gene, but several others are more than 16 kb 5' of the gene. Most patients with CLL and the t(14;19) also show trisomy 12.
Adult↗
Twice-weekly paclitaxel and radiation for stage III non-small cell lung cancer.
A phase I study was conducted to investigate the safety and efficacy of twice-weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and concurrent thoracic irradiation in patients with stage III non-small cell lung cancer. Radiation therapy beginning on day 1 was delivered in 1.8- to 2.0-Gy daily fractions, to a total dose of 61 Gy. Paclitaxel at a starting dose of 25 mg/m2/d was administered intravenously over 1 hour before daily radiation on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, and 39, for a total of 12 doses over 6 weeks. The paclitaxel dose was escalated by 5 mg/m2/d in each cohort of patients to determine the maximum tolerated dose. The highest paclitaxel dose reached was 40 mg/m2/d, as defined by dose-limiting toxicities of esophagitis and desquamation within the radiation fields. For each dose group, the median total number of paclitaxel doses administered was 12 and the median total radiation dose was 61 Gy. Response rates ranging from 50% to 100% were observed (three of six patients at paclitaxel 25 mg/m2, four of six at 30 mg/m2, seven of seven at 35 mg/m2, six of six at 40 mg/m2), for an overall response rate of 80%. We conclude that the maximum tolerated dose of paclitaxel is 35 mg/m2 given twice weekly in a 1-hour infusion for 6 weeks concurrently with thoracic irradiation. This study provides the basis for an ongoing trial combining twice-weekly paclitaxel and carboplatin with concurrent thoracic irradiation for patients with stage III non-small cell lung cancer.
Adult↗
The presence/absence of Bcl-2, Ca2+/calmodulin-dependent protein kinase IV, calretinin and p53 in baker's yeast and wheat germ.
After removing the nonspecific immunoreactivities from crude extracts of Saccharomyces cerevisiae and wheat germ by immunoaffinity chromatography, the presence of Ca(2+)-related proteins was tested by Western blot analysis. Immunoreactivity for Bcl-2 was absent in the yeast, whereas the immunoreactivity was evident in wheat germ and remained unchanged after incubation for 4 h with or without actinomycin D. Such incubation caused the degradation of immunoreactive-peptides of Ca2+/calmodulin-dependent protein kinase IV (CaMPK IV) in the yeast and wheat germ. Calretinin and p53 were absent in the yeast and wheat germ. The level of cyclic AMP in the yeast increased 100% after incubation for 30 min with actinomycin D. These results suggest that actinomycin D may not affect intracellular levels of these calcium-related proteins in the yeast and wheat germ, and that Bcl-2 occurs in multicellular eukaryotes. Moreover, the cellular level of CaMPK IV may vary during the onset of cell division and differentiation.
Antibodies, Monoclonal↗
Trisomy 10: age and leukemic lineage associations.
We observed three cases of acute leukemia with trisomy 10 (+10) as the sole abnormality, two were adult patients with ANLL (subtype M0 and M1 respectively), and the third that of a child with ALL. The literature describes nine additional cases, four with ALL (all of whom were children) and five with ANLL (all of whom were adults). Cell marker studies on the ANLL cases showed a common positivity for CD7 and CD33 in our two cases, as well as in four of the previously reported cases, whereas in ALL the only two informative cases were classified as early pre-B ALL. There appears to be an age-related pattern in the specificity of the leukemic lineage. Trisomy 10 appears to be associated exclusively with ALL in children and with ANLL (usually M0-M1) in adults. The prognosis appears to be also divided between the two groups, being good in the pediatric group and moderate in the adult group.
Aged↗
Urban hypothermia. Many elderly people cannot keep warm in winter without financial hardship.
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Aged↗
Parallel self-expanding covered metal stents in the trachea and oesophagus for the palliation of complex high tracheo-oesophageal fistula.
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Aged↗
Factors influencing plasma lipid profiles including lipoprotein (a) concentrations in renal transplant recipients.
Fasting plasma cholesterol, triglycerides, high-density lipoprotein (HDL) and apoprotein (apo) B were elevated in 214 nondiabetic renal transplant recipients when compared to a reference group. Apo (a) was slightly but not significantly lower in transplant recipients (median 118 mg/dl, range 16-1680 vs 130 mg/dl, 10-1176) and this difference could be predicted from Lp (a) isoform analysis. Cholesterol, triglyceride, apo B and apo (a) concentrations correlated negatively with creatinine clearance but none of these parameters showed a significant association with proteinuria. Patients treated with steroids had higher plasma HDL concentrations than those receiving cyclosporin monotherapy (P < 0.01). The use of diuretics was associated with raised triglycerides (P < 0.001) and cholesterol (P < 0.01) and with reduced HDL (P < 0.01) whilst patients receiving beta-blockers had significantly higher triglycerides (P < 0.01) and lower HDL levels (P < 0.02). In multiple regression analysis, age (P < 0.01), creatinine clearance (P < 0.05) and diuretic therapy (P < 0.005) were independent risk factors for increased cholesterol whilst apo (a) levels correlated negatively with creatinine clearance (P < 0.005). These results suggest that impaired renal function, steroids and non-immunosuppressive drugs contribute to lipid abnormalites in renal transplant recipients.
Adrenergic beta-Antagonists↗
A case of therapy-related extramedullary acute promyelocytic leukemia.
We report a patient with extramedullary acute promyelocytic leukemia (APL) occurring after radiation therapy for carcinoma of the prostate. To the authors' knowledge, this patient represents the first case of cytogenetically and fluorescence in situ hybridization (FISH) confirmed therapy-related extramedullary APL. In contrast to the majority of previously reported t-APL, this case underwent a very unfavorable course.
Aged↗
Unusual and unrelated polyclonality in a case of myeloid disease.
A case of myelofibrosis with myeloid metaplasia was found to have five cytogenetically unrelated clones in the marrow, four of these clones being abnormal. We present the hypothesis that the hematologic disease in this patient was caused by a genetic event not discernible microscopically (cytogenetically) and that the distinctive abnormal clones may have been generated at different anatomic sites.
Aged↗