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Biomedical subjects

K Cooper

Publications and source records attributed to K Cooper.

At least 55 records · Page 3Linked to original sources

Rheumatic Aschoff nodules revisited. II: Cytokine expression corroborates recently proposed sequential stages.

AIMS: A recent immunohistochemical analysis of the Aschoff lesions in rheumatic fever, combining immunohistochemical analysis with comparative morphology, permitted the division of the Aschoff nodules into three stages: (1) Aschoff nodule without admixed lymphocytes, (2) Aschoff nodules with a few T lymphocytes, and (3) Aschoff nodules containing many admixed lymphocytes of both B- and T-cell phenotype. It was postulated that the order of progression was from stage 1 with macrophages only, to accumulation of first T lymphocytes (stage 2) and then B lymphocytes (stage 3). This study was undertaken to determine the role and distribution of interleukin 1 (IL-1), interleukin 2 (IL-2) and tumour necrosis factor alpha (TNF alpha) in the various stages of the rheumatic Aschoff nodule to investigate our hypothesis on the progression of these nodules. METHODS AND RESULTS: Sixteen fresh valve specimens from patients with acute rheumatic fever undergoing valve surgery were obtained. Tissue sections from 14 specimens identified as containing Aschoff nodules were subjected to immunohistochemistry for (1) T and B lymphocytes, to stage the lesions according to our previously proposed criteria; (2) IL-1, IL-2 and TNF alpha; and (3) CD4 and CD8 to phenotype the T lymphocytes. The stage 1 and 2 lesions expressed IL-1 and TNF alpha in the macrophages. The stage 3 lesions showed more variable expression of all three cytokines including IL-2 within T lymphocytes. CONCLUSION: TNF alpha and IL-1 secretion in macrophages is required for T and B lymphocytes activation and aggregation; suggesting that macrophages arrive at the scene of rheumatic injury prior to the lymphocytes. IL-2 is usually expressed later in the inflammatory process and was found only in the lymphoid aggregates. This study therefore produces corroborative evidence for our previously proposed developmental stages of the Aschoff nodule.

Acute Disease

Adenoid cystic carcinoma of the salivary glands: a review of 10 years.

A retrospective analysis was performed of 50 patients with adenoid cystic carcinoma who were seen in the Department of Radiation Oncology, University of Witwatersrand, Johannesburg, South Africa, in the past 10 years. There were 25 men and 25 women with a mean age of 52 years (age range, 21 to 88 years). Five patients had metastatic disease, and 17 had neural invasion. Thirty-four patients had surgery (11, complete; 23, microscopic residual). Sixteen patients had radiotherapy as initial management. The disease-free survival was 26%, overall survival was 29%, and local control was 30% at 10 years. Most recurrences occurred in the first 3 years. Nine patients had metastasis following treatment. The mean survival after metastasis was 15 months. Seven prognostic variables were analyzed using the log-rank test. There was no impact of age, site, type of salivary gland (major vs. minor), tumor stage, node positivity, or neural invasion on disease-free survival, overall survival, or local control. Extent of surgical resection (complete vs. microscopic residual) had a significant impact on disease-free survival and local control (P < 0.05) but no impact on overall survival (P > 0.05) because of the slow-growing nature of these tumors. Similarly, patients who had microscopic residual after surgery and were treated with radiotherapy did better than those who had biopsy and radiotherapy, although this was not significant statistically (P > 0.05). Thus, whenever possible, every attempt must be made to remove all microscopic tumor by surgery. Addition of postoperative radiotherapy with high-energy photons did not improve the locoregional control or survival in our series. There is a place for neutrons in the treatment of adenoid cystic carcinomas in advanced cases of inoperable or recurrent tumors, as a review of literature shows.

Adult

Comparative analysis of biotin intranuclear inclusions of gestational endometrium using the APAAP, ABC and the PAP immunodetection systems.

AIMS/BACKGROUND: Intranuclear inclusions have been observed in gestational endometrial glands. Although resembling Herpes simplex virus infected cells, these nuclei have been shown to contain endogenous biotin. Hence, immunohistochemical systems using the avidin-biotin complex will result in cross reaction and false positivity. This study investigates a series of 10 gestational endometria (formalin fixed and paraffin wax embedded) with intranuclear inclusions using three different immunodetection systems with primary anti-biotin. RESULTS: Both the alkaline phosphatase anti-alkaline phosphatase (APAAP) and peroxidase anti-peroxidase (PAP) systems confirmed that the intranuclear inclusions were endogenous biotin. The streptavidin biotin complex (StreptABC) system produced a positive reaction in both test sections and controls (omitting primary anti-biotin) in the presence of prior blocking with free avidin and biotin. In addition, aberrant immunoreactivity was observed in adjacent nuclei/cytoplasm of endometrial glands and decidualised stroma in the negative control of the PAP system. This was subsequently eliminated using microwave pretreatment prior to immunohistochemistry. CONCLUSION: The use of either the APAAP or PAP immunodetection systems (the latter with microwave pretreatment) is recommended for any immunohistochemical or non-isotopic in situ hybridisation investigation undertaken on gestational endometria.

Biotin

Human papillomavirus and schistosomiasis associated bladder cancer.

AIMS: To determine the human papillomavirus DNA status of schistosomal associated squamous cell carcinoma of the urinary bladder in South Africa. METHODS: Twenty five archival samples of bladder squamous cell carcinoma associated with Schistosoma haematobium were subjected to non-isotopic in situ hybridisation and the polymerase chain reaction for the detection of human papillomavirus 6, 11, 16, 18, 31, and 33 genotypes. RESULTS: Using these two techniques, none of the 25 cases was shown to harbour human papillomavirus DNA. CONCLUSIONS: This study abrogates the role of human papillomavirus in schistosoma associated bladder carcinoma in South Africa. It is suggested that other factors including nitrosamine exposure, p53 mutation, and additional unknown chromosomal events play a major role in the development of this parasite associated neoplasm.

Carcinoma, Squamous Cell

Myxoma in the carotid artery. Myxomatous occlusion of internal carotid artery.

BACKGROUND: We describe a patient with an unusual cause of internal carotid artery occlusion resulting in a stroke. CASE DESCRIPTION: A 41-year-old woman presented with a typical acute right middle cerebral artery territory infarct. Her hematological and cardiological status was assessed, including all extracranial vessels. Carotid angiography and a biopsy were performed of the occluded right internal carotid artery and demonstrated a myxoma. Cardiac investigations to determine the source of the myxoma, including transthoracic and transesophageal echocardiograms, CT and yo-yo CT scans, and MRI of the heart, were normal. No residual tumor or potential source of the tumor was found. CONCLUSION: The cause of stroke was a myxomatous occlusion of the right internal carotid artery. An entire cardiac tumor may have embolized with no detectable residual tumor in the heart; alternatively, a myxoma may have originated as a primary tumor in the carotid artery. To our knowledge, no primary myxoma has been reported to have originated in a blood vessel.

Adult

A tool for assessing perineal trauma.

The initial aim of this study was to develop a reliable visual tool to assist in the assessment of the severity of oedema and bruising in perineal trauma, using a categorical scale of 'none', 'mild', 'moderate' and 'severe'. A standardised set of photographs was selected by 10 clinically experienced midwives to represent these categories. The tool was tested in a clinical trial involving 77 women, recording and monitoring changes in the level of oedema and bruising during the first 48 hours following suturing of an episiotomy. The results demonstrated a statistically significant change for both oedema and bruising. However, the less experienced assessors reported some uncertainties in assessing a small proportion of women. A combined method, using this tool with a categorical scoring scale, was used to minimise difficulties in the assessment. Two pairs of midwives, one pair very experienced in assessing perineal trauma and the other less experienced, evaluated the combined method. The results showed a high level of agreement. The standard set of photographs and categorical scoring scale together resulted in a reliable and sensitive assessment tool to evaluate severity of perineal trauma.

Adult

Exuberant fibroadenomatoid proliferation in a pulmonary mesenchymoma (hamartoma): report of a lesion mimicking a sclerosing pneumocytoma.

We report the cytologic and histopathologic features of an unusual peripheral primary lung tumor in a 61-year-old female. The central portion showed features of typical pulmonary chondroid hamartoma (mesenchymoma). Arising from the peripheral margin of this tumor, however, was an exuberant proliferation of papillary mesenchymal structures lined by type 2 pneumocates, mimicking papillary sclerosing hemangioma (pneumocytoma). This extreme example of fibroadenomatoid proliferation shares histologic features with other pulmonary neoplasms characterized by mesenchymal cores lined by type 2 pneumocytes. We propose that such lesions be unified under the term "alveolar mixed tumor".

Connective Tissue

Examination of baseline levels of carboxypeptidase N and complement components as potential predictors of angioedema associated with the use of an angiotensin-converting enzyme inhibitor.

OBJECTIVE: To determine if mean levels of complement components and carboxypeptidase N differed when comparing patients who exhibited angioedema following angiotensin-converting enzyme inhibitor therapy to those who received angiotensin-converting enzyme inhibitor therapy but did not have angioedema. DESIGN: Case-control study nested within an 8-week, open-label study of the use of quinapril hydrochloride for hypertension in 12275 patients. SETTING: Multicenter, with sites throughout the United States. PATIENTS: Of the 36 patients with angioedema described, 22 participated in the study. They were matched to 48 controls by age, sex, race, length of follow-up, and geographical region. INTERVENTION: All patients received quinapril therapy prior to participation in this case-control study. MAIN OUTCOME MEASURES: Levels of carboxypeptidase N, total hemolytic complement, C1 esterase inhibitor, and C4, along with questionnaire data, including a history of angioedema-like episodes and family history of angioedema. RESULTS: The 22 patients had significantly lower mean levels of carboxypeptidase N (kininase I) (P = .03) and C1 esterase inhibitor (P = .04) compared with the 48 matched controls, but all mean values were within normal laboratory ranges. A history of prior angioedema-like episodes was associated with an approximate 6-fold increase in the subsequent risk of angioedema following angiotensin-converting enzyme inhibitor therapy. CONCLUSIONS: Small differences in levels of carboxypeptidase N or C1 esterase inhibitor may contribute to an increased risk of angioedema with angiotensin-converting enzyme inhibitor therapy. Given the large overlap in the distributions of carboxypeptidase N and C1 esterase inhibitor levels, prior testing could not be used to evaluate angioedema risk for an individual patient considering angiotensin-converting enzyme inhibitor therapy. A history of prior angioedema-like episodes was associated with increased risk, but this result should be interpreted with caution because of possible recall bias.

Angioedema

Adenoid basal carcinoma of the uterine cervix: detection of integrated human papillomavirus in a rare tumor of putative "reserve cell" origin.

This study investigated the role of human papillomavirus (HPV) in adenoid basal carcinoma, a rare neoplasm of the uterine cervix. Nine archival paraffin-embedded tumors were analyzed with non-isotopic in situ hybridization (NISH) for HPV types 6, 11, 16, 18, 31, and 33 using digoxigenin-labelled probes. The polymerase chain reaction (PCR) was performed on each of the cases using E6 consensus primers to HPV. A total of 67% of adenoid basal carcinomas harbored the HPV genome with NISH, of which 3 were PCR-positive. Integrated HPV 16 DNA was demonstrated in 4 of the 6 NISH positive cases. Two cases showed integrated HPV 33. HPV DNA was not detected in the three remaining cases. These results show that the integrated high-risk HPV, in particular type 16, is associated with this uncommon cervical tumor.

Adult

Role of radiotherapy in stage III invasive thymomas.

Twenty-five patients with malignant invasive stage III thymomas who underwent biopsy for tissue diagnosis were treated with primary radiotherapy (mean dose 46.36 Gy, range 32.4-58 Gy). These patients were followed up for a period of 10 years and survival/failure analysis was performed. Five prognostic variables were compared using the log rank test. There was no difference in survival between ages less than 50 and more than 50 years, presence or absence of myasthenia gravis, sex, histology and race. The mean follow-up was 39 months (range 1-86 months). The 5-year disease-free survival was 81% overall survival 72% and local failure rate 13%. Most local failures occurred in the first 3 months. Six patients died after a course of radiotherapy (2 intrathoracic relapse, 1 disseminated disease, 1 local failure and distant metastasis, 2 causes not related to disease). Hilar fibrosis was seen in 4 patients who are asymptomatic. No other complications were recorded. Radical external beam radiotherapy alone can give good results in malignant stage III invasive thymomas.

Adult

Morphologic alterations in esophageal squamous cell carcinoma after preoperative high dose rate intraluminal brachytherapy.

BACKGROUND: Total esophagectomy specimens from 4 patients given preoperative high dose rate intraluminal brachytherapy (HDRILBT) of 20 Gray (GY) in 2 fractions of 10 Gy each week were reviewed for radiation changes. METHODS: In all patients, preoperative biopsy specimens showed moderate to poorly differentiated squamous cell carcinoma with minimal to negligible keratin production. The esophagectomy specimens were sampled at the resection margins, the edge of irradiated length, 1 cm from the proximal and distal edge of visible tumor, the center of the tumor, and the lymph nodes. RESULTS: Radiation change in the form of fibrosis was limited to the submucosa at the resection margins, the circular muscle layer at the edge of irradiated length, and full thickness at 1 cm from the edge of the visible tumor and the center of the tumor. Surface epithelium did not show any changes at the resection margins but did show basal cell hyperplasia at the edge of the irradiated length and ulceration at 1 cm from the edge of the visible tumor and the center of the tumor. Endarteritis obliterans was seen only 1 cm from the edge of the visible tumor and the center of the tumor. Necrosis, intense keratin formation, and giant cell reaction were observed at the center of the tumor. When compared with the preradiotherapy biopsies, the amount of keratin in the postradiotherapy specimens was extensive. HDRILBT may cause induction of the keratin gene in the irradiated cells to stimulate differentiation toward better differentiated cells. CONCLUSIONS: HDRILBT may cause the keratin gene in the irradiated cells to induce differentiation toward better differentiated cells. Preoperative high dose rate intraluminal brachytherapy may have a role in improving the prognosis of patients with early esophageal cancer treated with a combination of radiotherapy and surgery.

Adult

Radiofrequency catheter ablation of right ventricular outflow tachycardia in children and adolescents.

OBJECTIVES: The current study reviews the safety and efficacy of radiofrequency catheter ablation for the treatment of right ventricular outflow tachycardia in children and adolescents and describes a modified method for mapping the tachycardia focus. BACKGROUND: Although radiofrequency catheter ablation has proved highly effective for the treatment of supraventricular tachycardia during childhood and adolescence, its application in children with idiopathic right ventricular outflow tachycardia has been limited. METHODS: Six children (mean [+/- SD] age 10.6 +/- 2.4 years, range 6 to 16) with right ventricular outflow tachycardia underwent seven radiofrequency catheter ablation procedures. The mean tachycardia cycle length was 323 +/- 24 ms (range 300 to 360). Two multipolar catheters were positioned in the right ventricular outflow tract to map the tachycardia focus. RESULTS: Radiofrequency catheter ablation was successful in five (83%) of the six children (95% confidence interval 36% to 99%). At successful ablation sites, local endocardial activation time preceded the surface QRS onset by 46 +/- 5 ms (range 37 to 57), and there was concordance of the 12-lead pace map and the electrocardiogram (ECG) in 11 (one patient) to 12 ECG leads (four patients). One patient developed complete right bundle branch block during radiofrequency catheter ablation. There were no additional complications and no clinical recurrences over a mean follow-up period of 12.7 +/- 3.8 months (range 9 to 22). CONCLUSIONS: These results suggest that radiofrequency catheter ablation is a safe and effective treatment for right ventricular outflow tachycardia during childhood and adolescence. In addition, tachycardia mapping may be enhanced by use of a multipolar right ventricular outflow catheter technique.

Adolescent