The temporal distribution of suicides in Baton Rouge.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
F Campbell
Publications and source records attributed to F Campbell.
Normal colonic mucosa in hereditary non-polyposis colorectal cancer shows no generalised increase in somatic mutation.
Hereditary non-polyposis colorectal cancer (HNPCC) has recently been linked to germline defects of DNA repair genes. Colorectal tumours in HNPCC frequently show DNA microsatellite instability, but it is not certain whether this mutator phenotype occurs throughout the morphologically normal colonic mucosa. We have previously used the mPAS histochemical technique in human colorectal mucosa to identify a polymorphism for O-acetyltransferase activity that shows monogenic inheritance and to show that crypt-restricted loss of O-acetyltransferase activity in heterozygotes is due to somatic mutation. We have now used this histochemical technique to measure the somatic mutation frequency in the uninvolved colon of 12 heterozygous patients with HNPCC, 15 with ileocaecal Crohn's disease and 16 with sporadic colorectal cancer (CRC). HNPCC patients showed a significant increase in mutation frequency with age (Mann-Whitney U, P = 0.02). In HNPCC patients aged < 49 years the mean stem cell mutation frequency was significantly lower than in the slightly younger group of patients with Crohn's disease (0.8 +/- 0.9 x 10(-4) vs 3.5 +/- 3.3 x 10(-4), P < 0.01), probably reflecting an increased mutation rate relating to chronic mucosal damage in Crohn's disease. Although not statistically significant, the stem cell mutation frequency was slightly less in HNPCC patients > 50 years than in sporadic CRC cases (4.9 +/- 3.4 x 10(-4) vs 5.9 +/- 3.6 x 10(-4), P > 0.5). We conclude that germline defects in HNPCC do not result in a generalised increase in liability to mutation in normal colonic mucosa but that a second, somatic, event is required. We postulate that this second event occurs in crypt stem cells at low frequency, giving rise to scattered individual crypts composed of mutation-prone cells. The cells in these crypts are then at high risk of acquiring the mutations that lead to adenomas, and to rapid progression to carcinoma.
Adult↗
Racial variation in the O-acetylation phenotype of human colonic mucosa.
O-acetylated and non-O-acetylated sialoglycoproteins can be distinguished by the mPAS (mild periodic acid-Schiff) histochemical technique. Individual adults show one of three different patterns of staining of large intestinal mucosa: uniformly mPAS-positive, uniformly mPAS-negative, or mPAS-negative with scattered mPAS-positive crypts. To test our hypothesis that these variations are the result of a single autosomal gene (oat) polymorphism, we have studied the frequency of the three patterns of staining in a total of 435 adult colon specimens from six geographically separate populations: British, South African blacks, Icelanders, Japanese, Hong Kong Chinese, and Bahrainis. The distribution of the three types of staining fell into two groups. In Japanese and Chinese, uniformly mPAS-positive cases were much more frequent than uniformly mPAS-negative cases; this distribution differed significantly (chi 2, P < 0.001) from that in non-Sino-Japanese, where the uniformly mPAS-positive phenotype was much less frequently found than the uniformly mPAS-negative phenotype. In neither of the groups did the frequency of the three phenotypes differ significantly from that predicted for a single gene polymorphism by the Hardy-Weinberg law. The variation in staining patterns between populations is consistent with variation in frequency of a single polymorphic autosomal gene (oat) controlling O-acetylation of sialic acid, probably by an O-acetyl transferase enzyme. Loss of function mutation in the high acetylator gene (oata) in a colonic crypt stem cell in heterozygous individuals would account for the scattered discordant crypts. Gene frequencies for a variety of enzymes differ between the Sino-Japanese and non-Sino-Japanese races.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylation↗
Human colonic stem cell mutation frequency with and without irradiation.
Mild periodic acid-Schiff (mPAS) staining distinguishes O-acetylated from non-O-acetylated sialoglycoproteins. In human colonic mucosa, individuals possess one of three phenotypes: uniformly mPAS-positive (non-O-acetylated), uniformly mPAS-negative (O-acetylated), and negative with infrequent scattered positive crypts. This is due to a polymorphism in a single autosomal gene (oat). Discordant crypts have not been found in children's colons, suggesting that they result from somatic mutation in heterozygous individuals. We now present evidence to confirm this based on a study of radiation-induced changes. Comparison of mPAS staining of large intestinal mucosa from patients given radiation 4 weeks before surgery for carcinoma of the rectum with matched controls receiving surgery alone showed a similar phenotype distribution, but information irradiated patients showed an increased frequency of discordant crypts (irradiated vs. non-irradiated 14.5 +/- 8.2 x 10(-4) vs. 6.1 +/- 4.2 x 10(-4)). When these were classified as wholly or partially involved by the aberrant phenotype, the increase was most marked in partially involved crypts (7.5 +/- 4.5 x 10(-4) vs. 0.3 +/- 0.5 x 10(-4), Mann-Whitney U, P < 0.005). Two patients receiving radiotherapy many years before colectomy showed a very high total discordant crypt frequency but relatively few partially affected crypts. Studies of somatic mutation in colonic or small intestinal crypts following a single dose of mutagen in mice have shown early partial crypt involvement by the mutated phenotype and later complete crypt involvement.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
The Klippel-Trenaunay syndrome: a rare cause of hematuria requiring nephrectomy.
The Klippel-Trenaunay syndrome is a rare disorder in which the congenital vascular anomalies can affect the urogenital tract. Several cases of hemorrhage from the urogenital system have been reported in children with this condition. We report an upper renal tract hemorrhage in an adult, which required nephrectomy. To our knowledge this condition has not been reported previously in an adult with the Klippel-Trenaunay syndrome. We discuss the condition, and its diagnosis, treatment and relevance to the urogenital tract.
Adult↗
Carcinosarcoma in a bladder diverticulum.
A 47-year-old man presented with hematuria and dysuria. He was found to have a carcinosarcoma originating from a bladder diverticulum. He underwent a partial cystectomy and received postoperative chemotherapy. One year later, he presented with a large local recurrence and died shortly afterward. We believe this to be the second case of a carcinosarcoma originating in a bladder diverticulum.
Carcinosarcoma↗
Otitis media in early childhood and patterns of intellectual development and later academic performance.
Examined long-term associations between otitis media with effusion (OME) during the first 5 years of life and patterns of intellectual development from 3-8 years and academic performance after 3 years in elementary school. Fifty-five socioeconomically disadvantaged children were studied prospectively between birth and 8 years. OME history was routinely documented from birth through 5 years during well and illness periods. Two aspects of children's OME experience were examined in relation to developmental outcomes: timing (whether the OME occurred during infancy vs. preschool years) and nature (whether the OME tended to be recurrent or persistent). Although OME during the first 5 years of life was not related to patterns of overall intellectual development between ages 3 and 8 years, recurrent OME during infancy was a negative predictor of teachers' ratings of children's task orientation/distractibility in the classroom. Results are interpreted in the context of the growing OME literature.
Achievement↗
p53 immunostaining suggests that uterine carcinosarcomas are monoclonal.
The histogenesis of carcinosarcomas has intrigued pathologists for a long time and remains unresolved. Two main theories have been put forward, one suggesting that they are monoclonal, another suggesting that they are biclonal. Our study examined p53 immunostaining in 17 uterine carcinosarcomas (mixed Müllerian tumours) and found positivity in five (30%). There was no disparity in immunostaining between the epithelial and the stromal components in any of the 17 tumours. This concordance in every tumour would be very unlikely if carcinosarcomas are biclonal. However, it would be expected if carcinosarcomas are monoclonal.
Carcinosarcoma↗
Quantitative audit of the content of histopathology reports.
An audit of histopathology reports presents the problem that the output is textual and difficult to quantify. This makes the definition of an adequate report subjective and susceptible to observer variation. A procedure has been developed which allows the quantitative analysis of reports and facilitates the development of local reporting guidelines. A topic is selected; the auditor then lists the possible details that may be included in the report and notes how many reports from a sample include each detail. The results are discussed at a departmental meeting with the aim of agreeing on reporting guidelines. At a later date another sample of reports can be analysed for compliance with the guidelines and compared with the previous reports. Problems with compliance can be discussed further and at the audit meeting the guidelines may be amended appropriately, thus completing the audit cycle. This method of audit has the advantage that the results are quantitative and that the group discussion and re-examination of the guidelines has educational value.
Humans↗
Herpes zoster encephalitis in the elderly.
Explore the source record for details and available documents.
Aged↗
Sarcoid-like granulomas in primary renal cell carcinoma.
A case of renal cell carcinoma containing non-caseating epithelioid granulomas is described. These granulomas were indistinguishable from sarcoid granulomas microscopically. There was a clinical suggestion of sarcoidosis thirteen years prior to the excision of the tumour. The pathogenesis and significance of tumour-associated epithelioid granulomas are discussed.
Carcinoma, Renal Cell↗
Relationship between urinary and serum growth hormone and pubertal status.
Explore the source record for details and available documents.
Creatinine↗
T-lymphocyte responses to Pneumocystis carinii in healthy and HIV-positive individuals.
Pneumocystis carinii pneumonia (PCP) is a well-recognized cause of morbidity in patients with impaired T-cell function. In this study of cellular immunity to P. carinii, peripheral blood mononuclear cells from 25 HIV antibody-positive (HIV+) patients and 11 healthy individuals were stimulated in vitro with P. carinii antigen. The responding T-cell blasts were cocultured with autologous P. carinii antigen-pulsed macrophages to measure P. carinii-specific cytolytic T-lymphocyte activity (CTL). T-cell blasts from two healthy donors were used to generate P. carinii-specific clones by limiting dilution. T cells from HIV+ patients proliferated less to P. carinii antigen than T cells from healthy volunteers. In contrast, the level of specific cytotoxicity was identical in all groups when equal numbers of CTLs were used. Within the group of symptomatic patients, CTL activity was higher in those with a history of PCP (p = 0.033). Pneumocystis carinii antigen-specific T-cell clones proved to be CD4+ and MHC class II restricted; six of eight clones tested showed P. carinii-specific cytolytic activity. Cell-mediated immune response to P. carinii in healthy individuals include CD4+, class II MHC-restricted T cells with P. carinii-specific cytotoxicity. There is an increasing loss of P. carinii-specific proliferative responses in HIV+ patients as disease progresses, but a cytotoxic response is still detected in the absence of proliferation.
Adolescent↗
Intraoperative management of patients with heparin-induced thrombocytopenia.
For 11 patients with confirmed heparin-induced thrombocytopenia, we used reversible platelet inhibition with iloprost, a stable prostacyclin analogue, to permit safe heparin administration for cardiac (n = 9) or vascular (n = 2) operations. In vitro, iloprost (0.01 mumol/L) prevented both heparin-induced platelet aggregation and 14C-serotonin release in all patients. Therefore, intraoperatively, a continuous infusion of iloprost was started before administration of heparin and was continued until 15 minutes after administration of protamine. For cardiac patients, after heparin administration, the whole blood platelet count did not change (171,000 +/- 29,000/microL versus 174,000 +/- 29,000/microL, mean +/- standard error of the mean); no spontaneous platelet aggregation was observed, and plasma levels of the alpha-granule constituents platelet factor 4 and beta-thromboglobulin increased from 38 +/- 14 and 140 +/- 18 ng/mL to 591 +/- 135 and 235 +/- 48 ng/mL, respectively. Fibrinopeptide A levels actually decreased from 287 +/- 150 to 27 +/- 6 ng/mL. Furthermore, adenosine diphosphate-induced platelet activation was preserved, postoperative bleeding times were unchanged, and no heparin-related deaths occurred. Similar results were obtained in both vascular patients. We conclude that temporary platelet inhibition with iloprost now permits safe heparin administration in all patients with heparin-induced thrombocytopenia who require a cardiac or vascular operation.
Adult↗
Neonatal hypothyroidism: comparison of radioisotope and ultrasound imaging in 54 cases.
Fifty-four neonates with congenital hypothyroidism identified by the North East and North West Thames Regional hypothyroid screening programme between January 1985 and December 1987 were investigated with radioisotope (Tc99m) and ultrasound scans of the thyroid before treatment with 1-thyroxine was commenced. Compared with the radioisotope scans, ultrasound identified normally sited thyroid tissue in only 7 out of 10 cases, and ectopic thyroid tissue in only 5 out of 26 cases. Three out of 18 cases with no isotope uptake in the neck appeared to have normally sited tissue on ultrasound scan. We conclude that in our hands ultrasound of the neck is of only limited value in the assessment of young infants with congenital hypothyroidism.
Congenital Hypothyroidism↗
Disability: dealing with wheels.
Explore the source record for details and available documents.
Activities of Daily Living↗
Exchange-transfusion with pyridoxalated polymerized hemoglobin: effects on liver PO2.
To examine the efficacy of modified stroma-free hemoglobin in maintaining liver PO2, rats were exchange-transfused to hematocrit 10% using pyridoxalated polymerized hemoglobin (plp-polyHb, 10-12 g/dl) prepared from crystalline Hb. Following hemodilution, plasma Hb was 7.4 g/dl, and rats were normotensive. Mean liver PO2 was 3.4 vs 23.3 mm Hg in sham-exchanged controls. Other rats, hemodiluted similarly with 6% albumin or hydroxyethylstarch, were hypotensive and died. At 24 hours plasma Hb was 2.0 g/dl, indicating an intravascular half-life of approximately 16 hours. Hepatic PO2 was 12.4 vs 26.8 mm Hg in nonhemodiluted controls. Data provided by clearance of low-dose indocyanine green suggested reduced plasma volume and depressed liver blood flow. Scattered foci of midzonal hypoxic damage were observed in liver lobules. The basis for hypoxic injury is considered to be due in part to the acute restriction of oxygen supply induced by exchange-transfusion with plp-polyHb. The rate of loss of intravascular hemoglobin and diminished plasma volume could have contributed to oxygen insufficiency as well. Endotoxin present in the plp-polyHb was not a factor.
Animals↗