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Biomedical subjects

M J Cooper

Publications and source records attributed to M J Cooper.

At least 91 records · Page 5Linked to original sources
PubMed1990

Proarrhythmic effects of antiarrhythmic drugs.

Drugs that are described as antiarrhythmic drugs may actually aggravate arrhythmia in several ways and these are termed proarrhythmic effects. The most common type of proarrhythmia is a paradoxical increase in the frequency of episodes of the target arrhythmia. This type of effect had not been suspected until recently and has not been widely publicized. It is a phenomenon common to all antiarrhythmic drugs when they are used to treat arrhythmias based on a re-entrant mechanism (the most common mechanism of clinical arrhythmias). Different drugs vary in their tendency to produce this type of proarrhythmic response. These differences are explicable in terms of the relative effects of the drugs on refractoriness and conduction times in the re-entrant circuit. Proarrhythmic effects are most important in the treatment of ventricular tachycardias because recurrences are often fatal. Proarrhythmic effects on ventricular tachycardia can now be predicted at electrophysiological study before commencement of long-term therapy, and potentially dangerous treatment can be avoided. The key to proper treatment to proarrhythmia is to recognize that it is a drug-induced problem and to withdraw the offending drug.

Aged↗
PubMed1990

Beta 2-microglobulin expression in human embryonal neuroblastoma reflects its developmental regulation.

Class I major histocompatibility complex (MHC) antigen expression in neuroblastoma may play a role in the oncogenicity of this embryonal tumor of childhood. Since N-myc amplification in neuroblastoma tumors is associated with rapid tumor progression (33) and N-myc decreases Class I MHC antigen expression in rat neuroblastoma cells (21), we quantitated levels of N-myc mRNA and Class I MHC cell surface antigens in a panel of 24 human neuroblastoma cell lines. We found that N-myc expression is not invariably associated with low levels of beta 2-microglobulin (B2M) and Class I MHC antigen expression. As we considered that Class I MHC antigens may be regulated in association with the differentiation stage of the neuroblastoma tumor, we examined the expression of B2M during development of the human adrenal medulla, the tissue of origin of most neuroblastomas. We found that B2M is a marker of differentiated adrenal medullary cells, expressed late during the third trimester of development. Moreover, using morphological and immunological criteria, we found that B2M is expressed in differentiated tumor cells. These data suggest that the expression of B2M in neuroblastoma is associated with the stage of differentiation of the tumor cell and not N-myc expression. Furthermore, these findings suggest that neuroblastomas may correspond to the arrested differentiation of adrenal neuroblasts at different stages of development.

Adrenal Glands↗
PubMed1990

Abdominocervical (transhiatal) oesophagectomy in the management of oesophageal carcinoma.

Fifty-four patients have undergone abdominocervical oesophagectomy for oesophageal carcinoma as an alternative to a conventional transthoracic approach. Their median age was 69 years, with a range of 38-90 years, and 39 per cent of patients had chronic cardiorespiratory disease. Lymph node metastases were found in 80 per cent of patients and transmural tumour spread in 91 per cent. Median duration of operation was 2.2 h (range 1.75-6.0 h), and median transfusion requirement was 2.5 units (range 0-8 units). Respiratory complications were common (41 per cent) and caused all six postoperative deaths (11 per cent). Other complications were atrial fibrillation (26 per cent), transient recurrent laryngeal nerve palsy (11 per cent), cardiac failure (2 per cent), stroke (2 per cent), subphrenic abscess (2 per cent) and empyema (2 per cent). There were two anastomotic leaks (4 per cent), clinically manifest as temporary salivary fistulae. There have been 32 deaths from recurrent carcinoma, with a median duration of survival of 14 months (range 4-53 months). Fifteen patients are still alive, with a median survival of 16.5 months (range 3-49 months); the current 3-year survival rate is 10 per cent. All patients resumed normal swallowing after operation, but 11 of them developed anastomotic strictures requiring a median of three dilatations. Avoidance of formal thoracotomy by the abdominocervical approach may allow more rapid oesophagectomy without increasing the risk of postoperative death and gives a quality of palliation at least equivalent to that of conventional transthoracic oesophageal excision.

Adenocarcinoma↗
PubMed1990

A comparison of two doses of nizatidine versus placebo in the treatment of reflux oesophagitis.

Three-hundred and twenty-five patients with endoscopically verified oesophagitis entered a double-blind, randomized multicentre study that compared 300 mg nizatidine b.d., 300 mg nocte and placebo. The 6- and 12-week treatment responses were studied. Healing was defined as complete epithelialization of all oesophageal lesions. The healing rates were 40% in the 300 mg nizatidine b.d. group, 30% in the 300 mg nocte group and 26% in the placebo group at 6 weeks. The corresponding figures after 12 weeks of treatment were 50%, 44% and 34%, respectively. The healing rates were significantly different (P less than 0.05) between the high-dose nizatidine group and placebo only, both at 6 and 12 weeks. Despite a trend at both 6 and 12 weeks in favour of 300 mg nizatidine nocte compared to placebo, this was not significantly different. The most important factor for the outcome, apart from the treatment group, was the pre-entry severity of oesophagitis. The differences observed between treatment groups in healing rates, symptomatic relief, and antacid consumption appear to result mainly from the patients with moderate and severe oesophagitis upon entry. Nizatidine (300 mg) b.d. appeared to be safe and effective in the treatment of reflux oesophagitis.

Adult↗
PubMed1990

New technique for analysing conjugated bile acids in gastric juice.

A new technique of high performance liquid chromatography (HPLC) was developed for the analysis of conjugated bile acids in gastric juice. The assay is rapid, sensitive, and highly specific for bile acid conjugates over the range 30-10,000 mumol/l and is not affected by the presence of food. Ten patients with a variety of common upper gastrointestinal disorders underwent continuous gastric aspiration for 16 hours, including a fasting, post-prandial, and nocturnal period, and aliquots of aspirates were analysed every two hours by the HPLC technique for the six most prevalent bile acid conjugates present in human hepatic bile. Intragastric bile acid concentrations were lowest in the post-prandial period and highest in the early hours of the morning. Conjugated bile acid proportions, or profiles, varied considerably from patient to patient, but tended to remain uniform over time in individual patients. It is concluded that HPLC is superior to enzymatic techniques for the analysis of conjugated bile acids in the upper gastrointestinal tract.

Adult↗
PubMed1990

Histogenesis of the human adrenal medulla. An evaluation of the ontogeny of chromaffin and nonchromaffin lineages.

The authors previously evaluated the expression of a panel of chromaffin-related genes during histogenesis of the human adrenal medulla. In these studies, chromaffin and nonchromaffin adrenal neuroblasts were identified. To better characterize these nonchromaffin neuroblasts, the authors evaluated two additional markers: HNK-1, an antibody recognizing the migratory neural crest cell; and S-100, a protein expressed by sustentacular cells of the adrenal medulla. HNK-1 immunoreactivity was found in both chromaffin and nonchromaffin cell types at different times during development, marking the nonchromaffin lineage during the second trimester of gestation as well as the chromaffin lineage in the neonatal period. In addition, S-100 expression was noted in some nonchromaffin neuroblasts, and sustentacular cells were first identified at approximately 28 weeks of gestational age. These data suggest a model of human adrenal medullary histogenesis that incorporates the chromaffin, ganglionic, and sustentacular lineages known to constitute the adult adrenal medulla.

Adrenal Medulla↗
PubMed1990

Human neuroblastoma tumor cell lines correspond to the arrested differentiation of chromaffin adrenal medullary neuroblasts.

We have examined the hypothesis that nonhematopoietic malignancies may contain cells corresponding to those which occur during the differentiation of tissue precursors. Neuroblastoma, an embryonal tumor of the adrenal medulla, was studied because of its well described ability to differentiate both in vivo and in vitro. We examined the expression of four genes during development of the human adrenal medulla: tyrosine hydroxylase, chromagranin A, pG2, and beta-2-microglobulin. The sequential expression of these genes by adrenal neuroblasts marks successive stages during maturation of the chromaffin lineage. We also observed a population of neuroblasts during adrenal medullary development that did not express any of these four genes, suggestive of adrenal medullary cells differentiating along nonchromaffin lineage(s). We then evaluated 27 neuroblastoma cell lines for the expression of these genes and found that 24 expressed chromaffin markers, with 19 of these mimicking the pattern of gene expression found during development. Three cell lines did not express tyrosine hydroxylase, chromogranin A, or pG2, consistent with either a very undifferentiated neural crest cell or maturation along a nonchromaffin lineage. These data indicate that neuroblastoma tumor cells correspond to adrenal neuroblasts arrested during morphogenesis of the adrenal medulla and raise the possibility that malignant transformation of cells at different stages of tissue maturation may contribute to the diversity that characterizes tumors of solid tissues.

Adrenal Gland Neoplasms↗
PubMed1989

Comparison of immediate versus day to day variability of ventricular tachycardia induction by programmed stimulation.

The use of programmed stimulation to assess long-term oral antiarrhythmic drug efficacy for ventricular tachycardia is complicated by the fact that mode of ventricular tachycardia induction varies from day to day in the absence of drug therapy. The purpose of this prospective study was to assess whether mode of ventricular tachycardia induction is more reproducible within one study than from day to day. Thirty-nine consecutive patients with documented sustained ventricular tachyarrhythmias secondary to coronary artery disease underwent three inductions of ventricular tachycardia at 15 min intervals in the absence of drug therapy. A stimulation protocol in which the only major variable was the number of extrastimuli required for tachycardia induction was used. Subsequent day to day variability in mode of tachycardia induction was also assessed in the same patients at two further drug-free inductions at intervals of 5 +/- 2 days. The number of extrastimuli required for tachycardia induction was significantly more reproducible at the immediate repeat studies than from day to day (69% of patients versus 31%, p less than 0.01). From these data, probability tables were derived that show the likelihood that changes in inducibility at subsequent tachycardia inductions are due to chance. The QRS configuration of induced ventricular tachycardia was also more reproducible at the immediate studies (64% versus 26%, p less than 0.01). Basic electrophysiologic and stimulation variables differed over a significantly wider range from day to day than at the immediate studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Autonomous growth of a human neuroblastoma cell line is mediated by insulin-like growth factor II.

Insulin-like growth factor II (IGF-II) mRNA was increased in two of eight neuroblastomas and in eight of eight pheochromocytomas, tumors of the adrenal medulla that occur in childhood and adulthood, respectively. RNA encoding the type I IGF receptor, the receptor thought to mediate the mitogenic effects of IGF-I and IGF-II, also was uniformly expressed in these cells. To assess the role of IGF-II in the growth of these tumor cells, we have used the SK-N-AS cultured neuroblastoma cell line, which can be continuously propagated in mitogen-free medium, as a model system. Our results strongly suggest that IGF-II, synthesized by SK-N-AS cells and acting through type I IGF receptors, contributes to the autonomous growth of this tumor cell line. (a) SK-N-AS cells synthesized large amounts of IGF-II RNA and secreted greater than 50 ng/ml of IGF-II (as determined by specific radioimmuno- and radioreceptor assays). Little, if any, IGF-I RNA or immunoreactive IGF-I were detected. (b) SK-N-AS cells possess type I IGF receptors. (c) Exogenous IGF-I and IGF-II stimulated DNA synthesis in SK-N-AS cells, and this stimulation was abolished by a blocking antibody to the type I IGF receptor. (d) This anti-receptor antibody also abolished the multiplication of SK-N-AS cells in the absence of added mitogens. We conclude that IGF-II is an autocrine growth factor for SK-N-AS cells and suggest that this mechanism may contribute to the growth of some adrenal medullary tumors.

Adrenal Gland Neoplasms↗
PubMed1989

Neuropeptide Y expression distinguishes malignant from benign pheochromocytoma.

No reliable gross or microscopic features distinguish benign from malignant pheochromocytomas. The diagnosis of malignant pheochromocytoma is based solely on the presence of regional or distant metastases. This study evaluated the expression of neuropeptide Y messenger RNA (mRNA) in nine benign and 11 malignant pheochromocytomas and has found that neuropeptide Y mRNA was expressed in all nine benign tumors but in only four of 11 malignant tumors (P = .0084). These data suggest that the determination of neuropeptide Y expression in the evaluation of patients with pheochromocytoma may have prognostic significance.

Adrenal Gland Neoplasms↗
PubMed1989

The value of angiography in the surgical management of pancreatic disease.

Selective visceral angiography should help to determine the nature and extent of pancreatic lesions and their suitability for resection. Between 1980 and 1987 coeliac and superior mesenteric angiograms were obtained in 76 patients considered for pancreatic resection. Anomalous arterial anatomy was delineated in 25%. Among arterial abnormalities observed in 42 patients (55%), increased or decreased vascularity and displacement were of limited diagnostic value, but encasement correctly predicted cancer in 18 of 21 cases and irresectability in nine of these. When present (17%), invasion or occlusion of the portal or superior mesenteric vein was even more accurate, indicating cancer in 12 of 13 cases and irresectability in 11 of these. Hepatic metastases were only detected in 7 of 15 patients (47%). Overall, angiography confirmed the diagnosis in 54%, localised the lesion in 64% and correctly forecast irresectability in 58%. Misleading data were obtained in five patients. There were no complications.

Adolescent↗
PubMed1988

Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA.

Chromogranin A (CGA), also referred to as secretory protein I, is an acidic protein that has been detected in all neuroendocrine cell types examined and is often present in large amounts relative to other secreted proteins. For example, CGA comprises at least 40% of the soluble protein of the adrenal chromaffin granule, and it appears to be the major secretory protein in the parathyroid secretory granules. CGA complementary DNAs (cDNAs) from bovine adrenal and pituitary have recently been cloned and sequenced and found to be nearly identical. A region of bovine CGA has a high degree of amino acid sequence identity to pancreastatin, a recently isolated porcine peptide that inhibits glucose-induced insulin secretion. This suggests that CGA may be a prohormone. We have cloned and sequenced a human cDNA encoding CGA. This human CGA cDNA has an overall 86% nucleic acid identity to the bovine cDNA. Like the bovine CGA cDNA, the human cDNA has little homology to pancreastatin at the 5' region of this peptide but significant amino acid homology to the carboxyl-terminal portion of pancreastatin where the biologic activity resides. There is an area within the pancreastatin region of human CGA and porcine pancreastatin with a 70% amino acid identity to the calcium-binding moiety of the E-F hand proteins such as parvalbumin and oncomodulin. These data suggest that CGA and pancreastatin may both be members of a larger family of calcium-binding proteins.

Amino Acid Sequence↗
PubMed1988

Bile acid concentrations in the refluxate of patients with reflux oesophagitis.

Although reflux of bile acids has been implicated in the pathogenesis of reflux oesophagitis, attempts to document this in vivo have failed to detect more than trace amounts of bile acid in the oesophagus. To determine the bile acid composition of oesophageal refluxate, 45 patients with abnormal acid gastro-oesophageal reflux with oesophagitis and 10 controls had a size 14 Fr Salem sump tube positioned 5 cm above the lower oesophageal sphincter. Oesophageal contents were continuously aspirated and collected in aliquots every 2 h over 16 h. Fasting, postprandial, upright and supine (nocturnal) periods were assessed and total conjugated bile acids were measured by high pressure liquid chromatography with a sensitivity of 8 mumol/l. Conjugated bile acids were detected in 2 of 10 controls (maximum 40 mumol/l) and in 39 of 45 patients (87 per cent). Eleven patients had peak conjugated bile acid levels greater than 200 mumol/l, and these levels occurred exclusively during the supine (nocturnal) period. Median conjugated bile acid levels during daytime reflux were less than 20 mumol/l which was significantly lower than during nocturnal reflux (median 51 mumol/l, P less than 0.001). Conjugated bile acids are detected in the oesophagus of most patients with oesophagitis and may play a role in the pathogenesis of oesophagitis in some patients with nocturnal gastro-oesophageal reflux.

Adult↗
PubMed1988

Differences between patients with ventricular tachycardia and ventricular fibrillation as assessed by signal-averaged electrocardiogram, radionuclide ventriculography and cardiac mapping.

This study examined 65 patients with ventricular tachycardia or fibrillation late after myocardial infarction to determine whether they differed with respect to duration of ventricular activation in sinus rhythm and left ventricular ejection fraction. Patients with spontaneous ventricular tachycardia had a longer ventricular activation time in sinus rhythm than did patients with spontaneous ventricular fibrillation. This difference was detected with the signal-averaged electrocardiogram (ECG) (tachycardia 181 +/- 33 ms, fibrillation 152 +/- 23 ms, p less than 0.001) and at epicardial mapping (tachycardia 210 +/- 17 ms, fibrillation 192 +/- 17 ms, p less than 0.02). Left ventricular ejection fraction was lower in patients with spontaneous ventricular tachycardia (0.22 +/- 0.09) than in patients with spontaneous ventricular fibrillation (0.27 +/- 0.09) (p less than 0.05). The patients with both spontaneous and inducible ventricular fibrillation had a shorter ventricular activation time on the signal-averaged ECG (129 +/- 17 ms) and a higher ejection fraction (0.36 +/- 0.05) than did either patients with spontaneous ventricular fibrillation and inducible ventricular tachycardia (158 +/- 21 ms and 0.25 +/- 0.08, respectively, each p less than 0.01) or patients with both spontaneous and inducible ventricular tachycardia (181 +/- 33 ms and 0.22 +/- 0.09, respectively, each p less than 0.001). Of the patients with inducible ventricular tachycardia, presentation with tachycardia rather than fibrillation was associated with a longer ventricular activation time on the signal-averaged ECG (181 +/- 33 versus 158 +/- 21 ms, p less than 0.02) and a longer cycle length of inducible ventricular tachycardia (290 +/- 61 versus 259 +/- 44 ms, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Pulmonary artery origin of the left coronary artery: diagnosis by two-dimensional echocardiography, pulsed Doppler ultrasound and color flow mapping.

Five children, aged 0.2 to 6.7 years, with pulmonary artery origin of the left coronary artery proved by angiography underwent echocardiographic examination from 1985 through 1986. Prospective identification of this condition was achieved by two-dimensional echocardiography alone in two patients. Using a parasagittal plane from the second or third intercostal space, identification of the anomalous origin from the pulmonary artery was also possible in the other children on subsequent examination. In all of these studies the right coronary artery was considerably enlarged. The ratio of the diameters of the right coronary artery and the aortic root was 0.25 to 0.33 (normal 0.12 +/- 0.02). Flow mapping by color Doppler ultrasound in three children studied most recently and peripheral arterial or aortic root contrast echocardiography identified the site of entry of the coronary flow into the pulmonary artery. The flow disturbance was detected on the aortic surface of the pulmonary artery opposite the portion from where the flow from a patent ductus is usually identified. Pulsed Doppler ultrasound identified the flow disturbance in the pulmonary artery in only three of the children. The two youngest patients did not demonstrate turbulence on pulsed Doppler ultrasound, but they were not examined by color Doppler ultrasound. The accuracy of noninvasive detection of pulmonary artery origin of the left coronary artery by ultrasound is improved by the use of a combined echocardiographic approach.

Aorta↗