Temporomandibular joint movement. Evaluation of protrusive splint therapy with GRASS MR imaging.

Ten temporomandibular joints (TMJs) of 5 healthy volunteers and 19 TMJs of internal derangements in 16 patients with splint therapy were examined with MR imaging. T1-weighted images were obtained only in the closed mouth position, and gradient recalled acquisition in steady state (GRASS) images were obtained in active opening and closing phases, allowing a pseudodynamic display of TMJ movement. All patients received protrusive splint treatment. The usefulness of MR imaging to assess the efficacy of splint therapy was evaluated. Corrected disk position with the splint in place was clearly demonstrated in 9 TMJs, corresponding with elimination of reciprocal clicking. Ten other TMJs of anterior disk displacement without reduction showed uncorrected disk position by the splint. This information could confirm the therapeutic efficacy, or suggest other treatment alternatives. GRASS MR imaging can provide accurate and physiologic information about disk function in initial and follow-up assessment of protrusive splint therapy.


Decreased cardiac output in the critical care setting.

The specific aim of this exploratory, descriptive study was to demonstrate that the nursing diagnosis, decreased cardiac output, contains at least seven separate and specific components. Forty critical care nurses completed a questionnaire about seven different case studies, or vignettes. Each vignette reflected one of the following: myocardial injury, arrhythmias, decreased preload, myocardial ischemia, increased afterload, drug effects, and cardiac surgery alterations. Mean scores were used to validate the specific subcategories. Analyses of variance were used to demonstrate statistically significant differences among them. Six of the labels were supported, providing preliminary evidence for the validity of these components of decreased cardiac output.


CT appearances of normal and obstructed submandibular duct.

CT scans of 40 patients without pathology in the floor of the mouth or the submandibular glands were reviewed. Intraglandular ducts were visualized in 27 and extraglandular ducts in 3 patients. The CT appearances of dilated submandibular ducts are described in 4 patients with proven causes of obstruction. Widening of the narrow gutter between the mylohyoid and hyoglossus muscles in one scan level is a prominent feature. An intra- or extraglandular duct diameter of 3 mm or more indicates possible obstruction, and the CT images should be scrutinized to reveal the cause.


Diagnosis of aneurysm of superior thyroid artery by CT and MR imaging.

A 51-year-old man presented with a nonpulsatile anterior neck mass which suggested a thyroglossal duct cyst. At CT a small cystic mass was revealed. The mass contained a well-defined, crescent-shaped, low-density area with homogeneous contrast enhancement. On MR T2-weighted spin-echo and gradient-echo images the mass was as hyperintense as the neck vessels. Angiography and operation confirmed an aneurysm of the left superior thyroid artery with a mural thrombus.


Ultrasound guided tumour biopsy in the anterior mediastinum. An alternative to thoracotomy and mediastinoscopy.

To evaluate percutaneous ultrasound (US) guided tumour biopsy of the anterior mediastinum all patients scheduled for open mediastinal biopsy were considered for percutaneous biopsy during a 2-year period. US guided biopsy was chosen when CT had shown the tumour to be in contact with the thoracic wall. US guided biopsy was performed in 23 patients on 28 occasions. The procedure was technically successful in all cases and no complications occurred. In 27 of 28 cases the biopsy diagnosis was identical to the final diagnosis. In one patient with a malignant lymphoma a false diagnosis of connective tissue remnant was reached. US guided tumour biopsy of the anterior mediastinum is a safe, cost-effective and reliable method and a good alternative to the traditional biopsy techniques via mediastinoscopy or thoracotomy.


Bedside chest radiography using digital luminescence. A comparison between digital radiographs reviewed on a personal computer and as hard-copies.

The introduction of picture and archiving communicating systems is currently being evaluated in several institutions. We decided, as an intermediate step, to see if image quality after transferral to a personal computer (PC) is sufficient for the diagnostic needs in an intensive care unit. Seventy-five portable digital chest radiographs were studied both as hard-copies and on a monitor after transferral to a PC. Two chest radiologists and one anesthesiologist reviewed the examinations. Our intention was to evaluate if everything that is routinely checked by the anesthesiologist is demonstrable after electronic transfer to a local workstation. We found practically no difference between the performance of monitor and film for the whole material.


MR imaging of acute renal cortical necrosis. A case report.

MR imaging of a patient with acute renal cortical necrosis secondary to massive bleeding following an abortion is presented. The kidneys were enlarged with a high signal intensity observed in the renal cortex on both T1- and T2-weighted images. Follow-up MR imaging showed thinned renal cortex of low signal intensity on both pulse sequences representing renal cortical calcification which was confirmed on conventional radiography and CT.


Polyetiology of renal allograft dysfunction. Does calculation of the resistive index still make sense?

In 101 consecutive patients with renal allograft dysfunction a correlation of Duplex Doppler sonography (DDS) with histopathologic reports of simultaneously performed biopsies was made. Renal vascular impedance was estimated by calculating the resistive index (RI). A total of 290 different specific histologic diagnoses (mean 2.1 +/- 0.84 diagnoses/biopsy) was noted. With increasing time interval to transplantation, single diagnoses as cause of allograft dysfunction decreased. DDS could not reliably differentiate, exclude, or grade any of the common causes of renal allograft dysfunction like vascular and/or cellular rejection, chronic rejection, acute tubular necrosis, cyclosporin nephrotoxicity, relapse of glomerulonephritis and infection. Follow-up studies after established histologic diagnosis in 19 patients with persisting allograft dysfunction demonstrated a lack of sensitivity of DDS to significant superimposed causes of transplant malfunction. We conclude that biopsy is still necessary to direct proper therapy of renal allograft dysfunction.


Leiomyosarcoma in Poland's syndrome. A case report.

We describe a 56-year-old female with absence of the right pectoralis muscles, aplasia of the right breast, and skeletal deformities of the right hand, typical of Poland's syndrome. Following complaints of lower abdominal pain, a CT examination revealed an 8-cm mass in the right anterior pelvic wall. Surgical resection of the mass revealed a high-grade, poorly differentiated leiomyosarcoma. Poland's syndrome is known to be associated with a high incidence of leukemia but this is the first description of its association with leiomyosarcoma. Although we cannot exclude the possibility of a chance association, it is reasonable to assume that, similar to other syndromes with multiple congenital anomalies, the association with an increased incidence of malignancy is an integral part of the underlying genetic abnormality.


Nonresectable adenocarcinoma of the rectum assessed by MR imaging before and after chemotherapy and irradiation.

Thirty-four patients with nonresectable adenocarcinoma of the rectum, defined as tumor fixation at digital examination, were examined with MR. All 34 patients had, according to MR imaging, perirectal tumor growth. In 23 (68%) of the patients, the tumor has reached an adjacent organ. Eight of these patients had disturbances of the MR characteristics in the adjacent organ which proved to be due to overgrowth, i.e., to tumor invasion into these structures. In the remaining 15 patients, without disturbed MR characteristics, 7 had tumor overgrowth at laparotomy. When there was a visible space between the tumor and adjacent organs, there was no sign of tumor overgrowth at laparotomy, except in one case. In 24 patients, examined both before and after combined irradiation and drug therapy, tumor regression was registered after treatment. MR imaging seems to be useful in the assessment of resectability and to evaluate preoperative anticancer treatment in patients with nonresectable rectal carcinoma.


Anal sphincter size measured by endosonography in healthy volunteers. Effect of age, sex, and parity.

The anal sphincter muscles consist of the circular internal and external sphincters together with the sling-shaped associated puborectalis muscle. Ten men, 10 women with no vaginal deliveries, and 10 women with one or more vaginal deliveries were studied with anal endosonography using a 7 MHz multiplanar endoprobe. The thickness of the internal sphincter and the thickness, length, and cross-sectional area of the external sphincter were measured and related to age, sex, and parity. Reproducibility was assessed by similar measurements on different days in 10 volunteers. Anal sphincter size was the same in men and women and was not affected by the number of child births. Internal sphincter muscle thickness increased with age. Anal manometry and electromyography with an anal sponge were performed in all volunteers but the results did not correlate to any of the anal sphincter dimensions. Our conclusion is that although there are some limitations, endosonography can be used to determine the size of the anal sphincter muscles.


Thrombosed hemorrhoid mimicking rectal carcinoma at CT.

A 46-year-old man with cirrhosis and portal hypertension complained of lower pelvic pain. CT of the rectum raised a strong suspicion of a rectal tumor. However, rectal examination, anoscopy, direct rectoscopy, and, unfortunately, post-mortem dissection, failed to confirm its existence. Nevertheless, large flat hemorrhoids were evident. Review of the patient's chart disclosed the presence of large thrombosed hemorrhoids detected by rectal examination prior to the CT examination. It is suggested that rectal hemorrhoids be included in the differential diagnosis of rectal tumor shown by CT in patients with portal hypertension.


Hydatid disease of the spleen. Ultrasonography, CT and MR imaging.

Seven patients with hydatid disease of the spleen were examined by radiography, ultrasound, CT, and in one case MR imaging. The observations were confirmed by patho-anatomic findings except in 2 patients where high indirect hemagglutination tests confirmed the diagnosis. In one patient primary, and in the others secondary, echinococcosis of the spleen was assumed to be present. Secondary hydatid disease of the spleen was caused by rupture of liver cysts with abdominal and pelvic dissemination. Ultrasound and CT findings of the cysts and cystic calcifications are described. In one patient MR imaging indicated prolapse of a splenic hydatid cyst into the left hemithorax, confirmed by patho-anatomic examination.


Aberrant left gastric vein directly draining into left portal venous system. A case report.

A 66-year-old man with early gastric cancer and liver cirrhosis was diagnosed by preoperative angiography as having an aberrant left gastric vein communicating directly with the left lateral portal vein system. This communication was confirmed during operation for the gastric cancer. Our report is the first of an aberrant left gastric vein showing direct communication with the left portal vein system.


Bone marrow extension and pelvic bone marrow activity in alcoholic liver disease. A RES scintigraphic investigation.

Red bone marrow extension and increased central bone marrow activity were found in 21 patients with alcoholic liver disease investigated with scintigraphy of the reticuloendothelial system. The patients had no concurrent disease known to alter red bone marrow distribution. The bone marrow extension and the increased pelvic bone marrow activity may be explained as being secondary to a decreased radiocolloid uptake in the liver and could thus be a sign of decreased reticuloendothelial capacity.


Comparison of dual energy X-ray absorptiometry of the proximal femur with morphologic data.

Measurements of bone mineral density (BMD) of the proximal femur (including femoral neck, Ward's triangle and trochanteric region) were compared with the Singh index grading in 40 normal subjects (20 male, 20 female) and in 116 patients (18 male, 98 female) referred for assessment of possible osteoporosis. Additionally, the BMD and the Singh index of 12 cadaver specimens (6 male, 6 female) of the proximal femur were compared with each other and with the histomorphology of the femoral necks of the specimens. Although there was a good correlation of Singh index with BMD in the group of male patients with suspected osteoporosis and in the series of bone specimens, there was a poor correlation in the group of female patients as well as in the normal controls and in the patient population as a whole. There was also poor correlation of Singh index values with histomorphologic data, whereas the BMD measurements correlated well with the amount of calcified bone found histologically in the femoral necks of the bone specimens. We conclude that the Singh index cannot be used to predict BMD of the proximal femur accurately.


Pharmacokinetics of iopentol in patients with chronic renal failure.

Iopentol 350 mg I/ml was injected in doses of 265 to 533 mg I/kg b.w. (mean 417 mg I/kg b.w.) in 10 patients with advanced nondiabetic chronic renal failure (S-creatinine 672 +/- 259 mumol/l (mean +/- SD)). Urine (10 patients) and feces (7 patients) were collected at 24 h intervals for 5 days after the injection. The elimination of iopentol was delayed. Five days after injection a mean of 54% (range 35-79%) of the dose was recovered in urine, and 11% (0-20%) in feces. Mean elimination half-life was 28.4 h, about 14 times the half-life found in healthy volunteers. The apparent volume of distribution was 0.27 l/kg b.w., indicating distribution only to extracellular fluid. Using renal iopentol clearance as reference value, GFR was overestimated by 40 to 60% with iopentol total clearance, showing extrarenal elimination of iopentol. The difference was most pronounced in patients with low GFR. In conclusion, this study shows an extrarenal elimination of iopentol and demonstrates a substantial increase in the fecal elimination in patients with severe renal failure.


Addition of sodium to the nonionic contrast medium iohexol during coronary angiography in man. Lack of electrocardiographic or hemodynamic effects.

It has recently been claimed that lack of sodium in nonionic contrast media may increase the risk of ventricular arrhythmias during coronary angiography. Thus, the influence of sodium addition to the nonionic contrast medium iohexol was studied in 75 patients with severe coronary heart disease. The study design was randomized, parallel and double-blind, and iohexol was given either with or without addition of NaCl (28 mmol/l). Both formulations induced a transient drop in arterial blood pressure, and prolongation of the QT interval and QRS duration at 10 s only (p less than 0.01). The electrical QRS axis was significantly changed by the coronary artery injections after 10 s, but not later. No differences between iohexol with and without NaCl were observed for any of the variables studied. No serious arrhythmias were observed. Thus, the addition of NaCl (28 mmol/l) to iohexol did not influence the electrocardiographic or hemodynamic changes induced by iohexol during coronary angiography.


Granulocyte adherence after intravenous and intraarterial injection of ioxaglate or iohexol.

The effect of iohexol and ioxaglate on granulocyte adherence to nylon fibers was investigated with blood from 15 patients undergoing angiography, and from 24 patients undergoing excretory urography. Decreased adherence and increased numbers of granulocytes in the circulation were observed soon after injection of iohexol or ioxaglate in the aorta, or injection of ioxaglate i.v. Increased adherence and decreased numbers of granulocytes in the circulation were observed soon after injection of iohexol i.v. The differences were small soon after the injection of contrast media (CM). More pronounced decreased adherence and increased numbers of granulocytes were detected 2 and 5 hours after injection in the aorta for both CM.


Radiographic contrast media and release of neutrophil specific proteins in vitro and after intravenous injection.

The neutrophil granulocytes contain granules in which different proteins are present. When activated the neutrophils degranulate and thereby release some of these proteins to the surroundings. Some of these proteins are specific for this type of cell, e.g., lactoferrin and elastase. To investigate the influence of contrast media (CM) on this release, blood was incubated with diatrizoate, ioxaglate, iohexol, iodixanol, hyperosmolar saline, and hyperosmolar mannitol at different concentrations, and the amount of the neutrophil specific proteins lactoferrin and elastase were measured. Decreasing protein concentrations were observed for increased medium concentrations, suggesting that the degranulation process of the neutrophils was inhibited by the CM. The protein concentrations were lowest after incubation with the two ionic media diatrizoate and ioxaglate. Significantly decreased values of plasma lactoferrin were observed one min after i.v. injection of iohexol or ioxaglate in 82 patients undergoing urography. There was no significant difference between the two CM.


CT of the wrist in suspected scaphoid fracture.

Bone scan and sagittal projection CT of the scaphoid was performed in 10 patients with clinically suspected scaphoid fractures. The primary and follow-up plain radiographs were negative or equivocal for fracture. CT examination demonstrated scaphoid fracture in 7 patients and normal findings in 3. It is concluded that CT of the scaphoid can replace bone scan to diagnose or rule out fracture in institutions where nuclear medicine facilities are not available.


CT attenuation of normal liver parenchyma on delayed scanning with iohexol.

Twenty patients were examined with CT of the liver before, during, and 4 to 6 hours after i.v. administration of 60 g iodine (200 ml iohexol). The attenuation of normal liver parenchyma was measured. The mean attenuation of normal liver parenchyma on nonenhanced scanning was 62.6 HU and on delayed scanning 78.7 HU. It seems that iohexol is a suitable contrast medium for delayed scanning of the liver.


Suppression by retinoic acid of epidermal growth factor receptor autophosphorylation and glycosylation in cultured human head and neck squamous carcinoma cells.

The epidermal growth factor receptor (EGF-R) gene is overexpressed or amplified in various human squamous cell carcinomas, including those of the head and neck (HNSCC). Earlier we found that beta-all-trans-retinoic acid (RA) inhibited the growth and suppressed the aberrant squamous cell differentiation of several cultured HNSCC cell lines. Here we examined the effects of RA on the expression and function of EGF-R in two HNSCC cell lines, 1483 and 183, which exhibit distinct states of squamous cell differentiation, EGF-R mRNA levels, and responses to the growth inhibitory effects of RA. Treatment with RA (1 microM, 7 days) of the RA-sensitive 1483 cells decreased the level of EGF-R mRNA two- to four-fold and the binding of 125I-EGF to the cell surface by 30%-35%. In contrast, RA treatment of the 183 cells did not alter the EGF-R mRNA level or the binding of 125I-EGF. Other effects of RA on EGF-R structure and function were similar in both cell lines. RA did not alter the amount of immunoprecipitable [35S]methionine-labeled cellular EGF-R, 125I-cell surface labeled EGF-R, EGF-R internalization, or transforming growth factor alpha (TGF-alpha) mRNA. More important, RA treatment of both cell lines decreased EGF-R autophosphorylation activity detected in immune-complex-kinase assay by about three- and five-fold in the 1483 and 183 cells, respectively. Likewise, RA decreased the glycosylation of EGF-R in both cell lines. In the 1483 cells, RA suppressed the incorporation of either glucosamine or fucose by about 50%, whereas in the 183 cells RA suppressed the incorporation of fucose by about 80%. These results demonstrate that RA can modify the structure of the EGF-R by decreasing its glycosylation and suggest that these changes may suppress the autophosphorylation activity of the receptor kinase. The RA-induced changes in EGF-R do not correlate with the effect of RA on the growth of the cells but may be related to the suppression of squamous cell differentiation in the 1483 cells.


13-cis-retinoic acid and cancer chemoprevention.

Chemoprevention is the newest strategy for controlling and managing cancer. At present, the multistep character of epithelial carcinogenesis makes this disease process the most amendable to chemopreventive interventions, which occur in the postinitiation, preinvasive phases. Chemoprevention study has focused on oral carcinogenesis because of its excellent preclinical models, well-defined premalignant phase (leukoplakia), ease of monitoring, and link through field carcinogenesis to other epithelial carcinogeneses of the upper and lower aerodigestive tract. Retinoids, the derivatives of vitamin A, are the most-studied chemopreventive agents, and 13-cis-retinoic acid is the best-studied chemopreventive retinoid. Laboratory study of the newly discovered nuclear receptors of retinoic acid is closing in on the precise mechanism of retinoid action. Only 13-cis-retinoic acid, at high doses, has established chemopreventive activity, which is in suppressing oral premalignancy and preventing second primary head-and-neck tumors. Preclinical and clinical work in the other aerodigestive sites of the lung and esophagus are at an early phase of study with no conclusive results currently available. High-dose 13-cis-retinoic acid also has achieved significant activity in preventing invasive carcinomas of the skin. High-dose 13-cis-retinoic acid, however, is not ideal for widespread chemoprevention approaches because of its toxicity. The toxicity-to-risk balance is delicate and complicated.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidermal growth factor receptor as a target for therapy with antireceptor monoclonal antibodies.

The epidermal growth factor (EGF) receptor is a potential target for antitumor therapy. Recent studies from many laboratories have found that this receptor is expressed in high levels on a variety of human tumor cells. Furthermore, the EGF receptor has been implicated in autocrine stimulation of cell growth in a number of experimental studies. We have produced anti-EGF receptor monoclonal antibodies (MAbs), which block the binding of EGF and transforming growth factor alpha (TGF-alpha), and can prevent ligand-stimulated activation of EGF receptor tyrosine kinase. These MAbs have been useful in studies of EGF receptor function. Experiments utilizing the MAbs to block ligand binding have demonstrated that autocrine stimulation of EGF receptor phosphorylation can occur via an extracellular pathway, involving TGF-alpha-mediated activation of EGF receptor on the surface of the cell. The capacity of anti-EGF receptor MAbs to inhibit cell proliferation has provided evidence of an autocrine stimulatory pathway in cultures of malignant human skin, breast, colon, and lung cells. Growth of a variety of human tumor xenografts can be inhibited in situations where autocrine dependency is demonstrable in cell culture. Imaging studies with anti-EGF receptor MAb labeled with indium 111 (111In) demonstrated selective uptake in xenografts expressing high receptor levels. Based on these observations, a phase I trial was carried out with 111In-labeled anti-EGF receptor MAb 225 IgG1 in patients with advanced squamous cell lung carcinoma, a tumor that invariably expresses large numbers of EGF receptors. In the case of squamous lung carcinoma, there is evidence that overexpression of EGF receptors correlates with worse clinical stage and worse prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Systematic development of bombesin/gastrin-releasing peptide antagonists.

Several families of very potent bombesin (Bn) receptor antagonist analogues have recently been developed and their biological potencies evaluated in a number of in vitro systems including guinea pig and rat pancreatic acini and Swiss 3T3 cells. These studies showed that analogues can exhibit diverse properties ranging from full antagonists, partial agonists, or full agonists depending on the assay system and animal species employed. We have developed two classes of more potent, shorter chain antagonists based on [psi CH2NH(13-14)]Bn(6-14) and desMet14Bn(6-13)NH2 structures. [D-Phe6 psi Leu13-Leu14] Bn(6-14)NH2 was a potent antagonist (Ki 6nM) in Swiss 3T3 cells and guinea pig acini but exhibited 10% partial agonist activity and lower binding affinity (Ki 60 nM) in rat acini. The partial agonism could be eliminated by using p-Cl-Phe or D-Phe at the C-terminus and partially eliminated using D-4-Cl-Phe in position 6. With the antagonist [D-Phe6]Bn(6-13)NH2 (Ki 96 nM), alkyl substituents on the amide group increased affinity 25-fold with the propylamide being the most potent peptide (Ki 4 nM) in 3T3 cells or guinea pig acini. It did, however, have high 40% partial agonist activity in rat acini. Alkyl esters or hydrazide derivatives were, in contrast, pure antagonists in all systems tested with [D-Phe6]Bn(6-13)OMe having the highest affinity in all systems and also excellent in vivo properties. All of the potent antagonists examined had little affinity for neuromedin B--preferring bombesin receptors, which had entirely new ligand structure-activity relationships.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of neuropeptides on human lung and breast cancer cells.

We evaluated the effect of seven classes of neuropeptides [bradykinin, cholecystokinin 26-33 (CCK), neurotensin, arginine-8 vasopressin (AVP), tyr-4 bombesin (BN), somatostatin, and motilin] on 18 human lung cancer and four human breast cancer cell lines to determine the pattern of responses. Flow cytometric analysis of Indo-1 AM-loaded cells was used to quantitate the intracellular calcium response of individual cells produced by these peptides alone or in simultaneous or sequential combinations. All 18 lung cancer cell lines responded to one or more peptide classes with classic small cell lines displaying the greatest responsiveness, followed by variant small-cell lines and non-small-cell lung cancer cell lines. Breast cancer cell lines demonstrated little or no response to any peptide. There was great variability in the magnitude of response and pattern of response in individual cell lines and between cell lines. Bradykinin was the most potent peptide and produced responses in the largest number of lung cancer cell lines. Simultaneous administration of active peptides produced greater intracellular calcium release than single peptides, though in a less than additive manner. Response to each peptide was followed by a refractory period lasting several hours or more. The refractoriness was peptide-specific, implying that each peptide has a distinct pathway, at least at the receptor level. Bradykinin antagonists could abrogate the calcium response to bradykinin but not to other peptides. Similarly, specific peptide antagonists for CCK, BN, and AVP blocked the response for only their specific agonist.(ABSTRACT TRUNCATED AT 250 WORDS)


Differential stimulation of the growth of lung-metastasizing tumor cells by lung (paracrine) growth factors: identification of transferrin-like mitogens in lung tissue-conditioned medium.

Certain metastatic tumor cells successfully form metastases at particular organ sites, and their organ colonization properties cannot be explained by mechanical or anatomic factors. These tumor cells possess the ability to colonize such sites through preferential adhesion to organ microvessel endothelial cells, preferential organ invasion by expression of particular degradative enzymes and response to organ motility factors, and preferential organ growth by response to growth factors present at relatively higher concentrations in the target organ. The likelihood that target organ-associated growth factors exist and are important in metastatic colonization has been approached by studying the mitogenic effects of target organ extracts, fragments, or conditioned media on poorly and highly metastatic tumor cells that show organ preference of metastasis. We previously described the isolation of a major organ-derived (paracrine) growth factor from lung tissue-conditioned medium. Characterization of this mitogen has demonstrated that it is a transferrin or a transferrin-like glycoprotein, and antibodies to transferrin can remove significant growth activity from lung tissue-conditioned medium. Further demonstration of the existence and characterization of metastasis-associated organ (paracrine) growth factors and their receptors will be helpful in understanding the organ preference of metastasis.


Expression of prohormone processing enzymes in neuroendocrine and non-neuroendocrine cells.

The biosynthesis of many peptides thought to have autocrine or paracrine effects on cell growth requires a series of enzymatic steps. The level of expression of two of these posttranslational processing enzymes was compared in several endocrine and non-neuroendocrine cell lines. Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is a bifunctional copper- and ascorbate-dependent enzyme essential in the formation of alpha-amidated peptides. Carboxypeptidase H (CPH; EC 3.4.17.10) removes basic residues from the carboxyterminus of the products of endoproteolytic cleavage of prohormones and is generally essential in the formation of substrates for PAM. PAM messenger RNA (mRNA) and activity were detectable in both endocrine (AtT-20, GH3) and non-neuroendocrine (L, 3T3, COS, BRL, C127) cells. Except for BRL cells, CPH mRNA and enzymatic activity were detectable in all the cell lines. BRL cells contained no detectable CPH mRNA and had a different carboxypeptidase B-like activity. Thus, expression of secretory granule-associated processing enzymes is not limited to cells of a classic neuroendocrine phenotype.


Control of tumor cell biology through regulation of peptide hormone processing.

Control of the biology of individual cells, organs, and organisms is achieved through an interplay of a host of specific interactions, many involving peptide hormones as modulators or effectors. In tumor cells these processes may result in uncontrolled growth as a consequence of autocrine and/or paracrine growth effects. Most peptide hormones are bioactive only after processing of the precursor prohormone by posttranslational processing enzymes. The enzymes involved with the production of bioactive peptides, in particular those associated with peptide alpha-amidation, provide potential targets for disruption of posttranslational processing mechanisms as a means of regulation of the progression of tumor cells. This information provides a rational basis for consideration of inhibition of autocrine neuropeptide synthesis as a strategy for chemointervention.


Biomarker intermediate endpoints and cancer prevention.

Detection of cancer is the definitive endpoint in the conduct of chemoprevention trials. There are, however, several reasons why cancer as the endpoint may not be feasible or ethical: 1) the usage of patients with easily followable preneoplasias may preclude the development of cancer, and 2) the time to a cancer event may be long or the incidence uncommon, even in individuals at high risk. Two major types of biomarker intermediate endpoints should be considered: 1) those that identify individuals at high risk and 2) those that serve as a surrogate for cancer. Various epidemiologic features, including family history, have been used to estimate relative risk. This approach, however, only slightly decreases the size of populations needed for chemoprevention trials and only little addresses the question of individual risk. Advances in understanding the genetic basis for cancer will lead to the development of probes that will help assess risk for many cancers. Innumerable biomarker intermediate endpoints can be identified as associated with cancer formation, including genetic, epigenetic, and histologic features. The challenge is not in identifying potential biomarker intermediate endpoints but in showing that they are relevant. Carcinogenesis has been shown to be carcinogen, inhibitor, dose, tissue, and species specific; it is likely that relevant biomarker intermediate endpoints will need to be identified, studied, and verified in human models. The upper aerodigestive system should be a rich source for biomarker intermediate endpoint studies, as tissue is readily available, the carcinogenic process can be monitored, and there are currently available reasonable compounds to use in biomarker intermediate endpoint modulation and chemoprevention trials.(ABSTRACT TRUNCATED AT 250 WORDS)


Rational targets for the early detection of lung cancer.

The fact that routinely effective treatments for disseminated lung cancer are not available has prompted the search for effective early detection systems. It is important to identify lung cancer while it is still confined to the bronchial epithelium and is potentially curable with local modalities. We have previously reported on an immunologically based assay to identify antigens expressed on shed bronchial epithelial cells. This assay resulted in a statistically significant correlation of immunostaining with the eventual development of lung cancer 2-4 years prior to routine clinical detection. Attempts to further improve this approach require an understanding of the basis for its success. Based on the work of Hakomori and coworkers, this difucosylated Lewis X structure would be a likely marker of carcinogenic transformation of the bronchial epithelium. In fact, an antibody to this structure was useful for sputum immunocytochemistry analysis for early lung cancer detection. Other carbohydrate structures would also be reasonable markers to evaluate for early detection application, based on the known pattern of expression of these structures in fetal, dysplastic, and neoplastic lung tissue. Another antibody used for sputum immunostaining recognizes a 31-kd protein structure; the antibody is not a known member of a likely class of early detection targets. The reported cases of lung cancer missed by the immunostaining approach included principally adenocarcinoma of the lung, suggesting that the addition of a marker(s) of that type of morphologic differentiation should be considered. Markers to dissect the various forms of lung adenocarcinoma are being characterized and are available for evaluation in early detection applications.(ABSTRACT TRUNCATED AT 250 WORDS)


Role of biology and prevention in aerodigestive tract cancers.

Primary prevention aimed at smoking control and chemoprevention for high-risk persons or patients at risk for a second cancer provide strong potential for cancer prevention and control of aerodigestive cancers. The National Cancer Institute (NCI) has a major effort to build this area of research. The Third Upper Aerodigestive Tract Cancer Task Force Workshop, held in 1989 under the auspices of the National Cancer Institute's Organ System Program, reviewed the opportunities for chemoprevention research on aerodigestive epithelial cancers such as the regulation of growth and differentiation in normal and malignant cells. The chemoprevention program's drug development effort is evaluating several promising candidate agents for future clinical testing and the NCI clinical intervention program is supporting several trials of selected chemoprevention agents with demonstrated potential for inhibiting cancers of the lung, bronchus, oral cavity, and esophagus. Of special interest to this program is the assessment of beta-carotene, retinol and related synthetic retinoids, and several vitamin and mineral combinations under study in high-risk international populations. Chemoprevention in the medical setting is a major focus of NCI's Community Oncology Program (CCOP), a network designed not only to increase accrual of patients to trials but also to speed adoption of state-of-the-art therapies. Public health strategies are directed toward control of exposure to tobacco. The focal point for these activities is NCI's Smoking, Tobacco, and Cancer Program (STCP). STCP smoking cessation efforts are targeted at specific populations that are at greater risk for developing cancer including youth, minority and ethnic groups, women, smokeless tobacco users, and heavy smokers. Two of the world's largest controlled intervention trials conducted by the STCP are underway: the Community Intervention Trial for Smoking Cessation (COMMITT), which focuses on 6.5 million heavy smokers in 11 pairs of matched communities in North America, and the American Stop Smoking Intervention Study (ASSIST), a coalition model designed to reach millions of Americans through existing health promoting systems.


Early events in the neoplastic transformation of respiratory epithelium.

The complex process of epithelial carcinogenesis is composed of discrete biologic events including the early activation events of "initiation" and "promotion." For lung cancer, these events are only now being elucidated. Despite the identification of possible target genes and their mutations, the "initiation" events for lung cancer remain poorly understood. The identification of these "initiation" events is a crucial step toward the development of practical molecular markers for early detection of this disease. The reversible process of tumor promotion remains somewhat enigmatic but is a promising target for chemoprevention. A wide range of substances, including asbestos and various substances in cigarette smoke, behave as tumor promoters for lung cancer. They appear to promote tumor formation by inducing cellular proliferation mediated in part by growth factors. The intracellular signals these factors provide are ultimately translated into cellular growth via steps involving nuclear transcription factors. Early response genes such as the jun and fos gene family members encode such nuclear transcription factors which are expressed in lung cancer cells and primary bronchial epithelial cells. The expression of these transcription factors is highly responsive to stimulation by growth factors including serum, transforming growth factor, and gastrin-releasing peptide. A more thorough understanding of this process will allow the development of molecular and/or pharmacologic antagonists that can interfere with the biologic process of tumor promotion and therefore function as chemoprevention agents.


Animal models for chemoprevention of respiratory cancer.

Of the several models for lung carcinogenesis, two appear appropriate for chemoprevention studies based upon dose response, tumor type, and tumor localization. One model utilizes the direct-acting carcinogen methylnitrosourea (MNU), and the other utilizes a carcinogen (diethylnitrosamine) requiring metabolic activation. Tumors appear rapidly in both models (within 6 months), and the model systems are responsive to modulation by several classes of potential chemopreventive agents. For example, the retinoid N-(4-hydroxyphenyl) retinamide reduces the incidence of lung adenosquamous carcinoma, but retinol or beta-carotene are ineffective when administered alone. However, concomitant administration of these compounds reduces the incidence of non-neoplastic dysplasias as well as adenosquamous carcinomas of the lung. In the MNU system, retinoids in general have been ineffective in reducing the incidence of tracheobronchial squamous-cell carcinomas.


Chemopreventive studies in Barrett's esophagus: a model premalignant lesion for esophageal adenocarcinoma.

Barrett's esophagus is a premalignant lesion in which the lower esophagus is lined with metaplastic columnar epithelium rather than the normal stratified squamous epithelium. It is a precursor lesion for adenocarcinoma of the esophagus. We are studying Barrett's esophagus as a model premalignant lesion for adenocarcinoma from the standpoint of identifying biologic markers of increased cancer risk as well as therapeutic strategies for eradicating the lesion. Ornithine decarboxylase (ODC) activity in Barrett's mucosa was significantly higher than in normal adjacent mucosa from the same patient. However, polyamine content was not significantly altered, suggesting dysregulation of the polyamine pathway. Flow cytometry is being used to assess the presence of aneuploidy and its significance in a premalignant lesion. Initial results have demonstrated that aneuploidy and dysplasia can be discordant. Cytogenetic analysis using short-term epithelial cultures established from endoscopic biopsies of the lesion has demonstrated the presence of clonal karyotypic abnormalities. The clinical significance of aneuploidy and abnormal karyotype, however, remains to be proved. Chemopreventive intervention trials have included use of 13-cis-retinoic acid. Considerable toxicity was encountered, and the lesion showed no change in extent in 11 evaluable patients. A subsequent clinical trial with a biologic endpoint used alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, to test whether a low dose could produce changes in polyamine content in gastrointestinal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)


Tumor antigen phenotype, biologic staging, and prognosis in head and neck squamous carcinoma.

Prior studies of alterations in tumor expression of normal blood group antigens and A9/alpha 6 beta 4 integrin, an extracellular matrix receptor, have suggested that these immunohistologic markers reflect the biologic aggressiveness of head and neck squamous carcinomas. To confirm these preliminary observations, prospective long-term follow-up of 82 previously untreated head and neck squamous carcinoma patients was performed. All patients were treated with conventional therapy. Median follow-up was 57 months. Tumor immunohistology for ABH blood group and A9/alpha 6 beta 4 integrin expression was performed and correlated with measures of host cellular immunity, disease-free survival, and overall survival. Loss of blood group expression and high A9/alpha 6 beta 4 integrin expression were each directly related to an increased frequency of early tumor recurrence. The combination of both variables was significantly associated with both disease-free (P = .029) and overall survival (P = .05). Increased expression of A9/alpha 6 beta 4 was associated with impaired T-lymphocyte function (P = .005), and loss of blood group expression was associated with decreased peripheral blood levels of CD8+ T-lymphocytes (P = .013). The findings suggest that these phenotypic characteristics of antigen expression in head and neck squamous carcinomas are important markers of biologically aggressive cancers and impaired host immune response. The clinical use of these biologic staging parameters in the initial assessment of patients should allow selection of more aggressive primary treatment strategies for individual patients.


Regulation of expression and phosphorylation of A9/alpha 6 beta 4 integrin in normal and neoplastic keratinocytes.

The A9 antigen is a basement membrane antigen of normal squamous epithelial cells that is strongly expressed in many squamous carcinomas. High expression of this antigen is associated with early relapse in squamous cell carcinomas of the head and neck. We now know that the A9 antigen is structurally, immunologically, and functionally similar to the alpha 6 beta 4 integrin that has been shown to be linked to metastatic behavior in murine tumor models. The alpha 6 and beta 4 genes have been cloned and sequenced, and a model has been constructed from the deduced amino acid composition. In this study we present a hypothetical model and use it to design experiments to assess the factors that influence the expression of the A9/alpha 6 beta 4 integrin in normal and malignant keratinocytes. High calcium induces down regulation of A9/alpha 6 beta 4 antigen in normal but not malignant keratinocytes within 24 hours. Although calcium can down-regulate beta 4 message in tumor cells in the absence of epidermal growth factor (EGF), transcription of beta 4 increased in the tumor cells under the conditions we used for assessing antigen expression (calcium plus EGF). Retinoic acid also stimulated transcription of beta 4 in tumor cells, but this was partially inhibited by the presence of high calcium. Phosphorylation of the beta 4 chain was stimulated by epidermal growth factor and calcium in normal keratinocytes, but in the malignant cells phosphorylation was constant regardless of the culture conditions. Our results indicate that high expression of the alpha 6 beta 4 integrin is associated with conditions that favor migration and undifferentiated proliferation of normal keratinocytes and that malignant keratinocytes differ from normal keratinocytes by constitutive phosphorylation of beta 4 and by failure to downregulate beta 4 transcription in response to calcium in the presence of EGF.


Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich Mild Heart Failure Trial.

Neurohormonal activation has major impact on the pathophysiology of congestive heart failure. The Munich Mild Heart Failure Trial was designed to test the hypothesis that interference with the renin-angiotensin system by angiotensin converting enzyme inhibition favourably influences the natural history of heart failure. 170 patients, median New York Heart Association (NYHA) class II, were randomised to double blind treatment with 25 mg captopril twice a day or placebo in addition to standard treatment for a median observation period of 2.7 years. Progression of heart failure to NYHA class IV on an optimally adjusted standard treatment, death due to progressive heart failure, and sudden death. Heart failure progressed to class IV in nine patients (10.8%) treated with captopril and in 23 patients (26.4%) treated with placebo (p = 0.01). The mean survival time until this end point was 223 days longer in the captopril group (Kaplan-Meier life table analysis; p = 0.02). Also, progressive deterioration to severe heart failure was a powerful predictor of total mortality and death from heart failure; 80% of deaths due to progressive heart failure occurred after this end point. There were fewer deaths caused by progressive heart failure in the captopril group than in the placebo group (4 v 11; p = 0.10) but similar numbers of sudden deaths (11 v 10). Progressive heart failure was the cause of death in 18.2% of all deaths in the captopril group and 50% in the placebo group. Total heart failure events (the end point on which power calculation was based) were also more common in the placebo group (19 v 32 events) but not significantly so. Total mortality was similar to both groups (22 of 83 v 22 of 87). Angiotensin converting enzyme inhibition in conjunction with standard therapy early in the course of congestive heart failure slowed the progress of heart failure and thus favourably altered the natural history of the disease.


Limitations of transoesophageal echocardiography in patients with focal cerebral ischaemic events.

To investigate the detection rate of cardiac sources of embolism by transoesophageal echocardiography in patients with focal cerebral ischaemic events and to relate the echocardiographic findings to other clinical findings. Prospective study with blinded analysis of the echocardiographic data and subsequent comparison with the other clinical findings. Regional cardiothoracic unit based in a teaching hospital. 131 consecutive patients with focal ischaemic cerebral events (49 with a transient ischaemic attack, 77 with a cerebrovascular accident, and five with a retinal arterial embolus) referred for echocardiography. Full M mode, cross sectional, Doppler, and contrast echocardiography by both the precordial and transoesophageal techniques. Precordial echocardiography detected a cardiac abnormality in 72 patients. Transoesophageal echocardiography confirmed all the precordial findings (except left ventricular hypertrophy, which at present cannot be defined with this technique) and detected other abnormalities in a further 20 patients (18 with potential right-to-left shunts and two with valve vegetations). It also showed spontaneous contrast echoes in 27 of 28 patients with a large left atrium and showed atrial thrombus in three. Cardiac abnormalities were clinically detected in 53 patients, all of which were confirmed or documented by echocardiography. In the 78 patients with no clinically detectable cardiac abnormality six had mitral valve prolapse and one had a regional wall motion defect (identified by precordial echocardiography) and 17 had potential right-to-left shunts (11 of which were identified only by transoesophageal echocardiography). Transoesophageal echocardiography is more sensitive than precordial echocardiography in detecting potential sources of embolism in these patients. However, except for the detection of a potential right-to-left shunt, the yield in patients with no cardiac abnormality is low. Moreover, the abnormalities detected in those with previously detected cardiac disease merely confirm the clinical diagnosis. Patients with left atrial spontaneous contrast echoes may benefit from anticoagulation but this requires further study. Until more data are available on this feature and on the role of potential right-to-left shunts in this population, the contribution of echocardiography, precordial or transoesophageal, remains limited.


Variable patterns of ST-T abnormalities in patients with left ventricular hypertrophy and normal coronary arteries.

Classically, the ST-T configuration in the electrocardiogram of patients with left ventricular hypertrophy is said to have a typical pattern of ST depression together with asymmetrical T wave inversion (the so-called left ventricular strain pattern). However, many patients with left ventricular hypertrophy may also have ischaemic heart disease. To revise the electrocardiographic criteria for left ventricular hypertrophy the ST-T configuration in patients with left ventricular hypertrophy documented by echocardiography and with normal coronary arteries was assessed. 24 patients were selected for this study. All had left ventricular hypertrophy documented by echocardiography, normal coronary arteries by cardiac catheterisation, and ST and/or T wave abnormalities in the lateral leads of their electrocardiogram. There were eight patients with aortic valve disease and 16 with hypertension who had coronary angiography as part of an investigation into the risk factors of sudden cardiac death caused by hypertensive left ventricular hypertrophy. No patient was receiving digitalis preparations or had electrolyte disturbances, and none had a previous myocardial infarction or ventricular conduction defect. Typical electrocardiographic evidence of left ventricular strain was found in approximately two thirds (63%) of patients and 95% of this subgroup had asymmetrical T wave inversion. Flat ST segment depression, with or without T wave inversion or isolated T wave inversion (symmetrical or asymmetrical) in the anterolateral leads, was seen in the remaining 37% of patients. These findings indicate that left ventricular hypertrophy without coronary artery disease can cause variable types of ST-T abnormalities in the anterolateral leads including the typical left ventricular strain pattern and non-specific ST-T changes. Non-specific abnormalities could not be distinguished from those of coronary artery disease and may adversely affect the accuracy of the electrocardiographic criteria for the diagnosis of left ventricular hypertrophy because they do not accord with the criteria for left ventricular strain.


Negative extrathoracic pressure ventilation for phrenic nerve palsy after paediatric cardiac surgery.

To investigate the feasibility of negative extrathoracic pressure ventilation as a respiratory support following phrenic nerve palsy after cardiac surgery. An uncontrolled pilot study. 14 patients aged one week to 30 months (median 5.3 months) with phrenic nerve palsy diagnosed by phrenic nerve conduction tests and diaphragmatic electromyograms. Four had bilateral and 10 unilateral palsy. Before treatment all required oxygen and 10 were receiving positive pressure ventilation. One of the patients with bilateral and four of the patients with unilateral palsies had undergone a plication before negative pressure ventilation was started. Treatment was started 6-65 days (median 23) after operation with a newly designed system which included a Perspex chamber, which gave easy access to the child, and an elastic latex neck seal. Continuous negative pressure was used in conjunction with intermittent positive pressure ventilation while continuous or intermittent negative pressure ventilation was used in extubated infants. All four patients with bilateral palsy survived with long-term intermittent negative pressure ventilation and did not require further surgery. Of the 10 with unilateral lesions, seven required no further surgery, two underwent plication, and one had a re-plication. Three patients with unilateral palsy died of non-respiratory causes. The duration of positive pressure ventilation after starting negative pressure ranged from 0 to 23 days (median 6). Treatment with negative pressure lasted for 3-241 days (median 32) and was predominantly administered off the intensive care unit, including at home. Negative pressure ventilation may be an alternative to positive airway pressure ventilation in the management of phrenic nerve palsy. A multicentre randomised controlled trial is now required to assess further the role of negative pressure ventilation in phrenic nerve palsy.


Cross sectional and Doppler echocardiographic evaluation of aortopulmonary shunts.

Shunt vessels were imaged and shunt flow was analysed by cross sectional and Doppler echocardiography in 12 patients who had had 14 shunt procedures (nine left Blalock-Taussig shunts, three right Blalock-Taussig shunts, one modified Waterston shunt, and one central shunt). The shunt vessels were classified by echocardiography as uniformly patent, segmentally stenosed, and uniformly stenosed. These findings were compared with those of angiography. Also the peak flow velocities at the aortic and the pulmonary ends of the shunt vessels were measured by Doppler echocardiography and the ratio of these values was calculated for each shunt. Twelve (85.7%) of 14 shunt vessels were imaged along their entire length by cross sectional echocardiography. The two remaining shunt vessels were only partially imaged. In 10 patients who also had angiography the echocardiographic and angiographic images of the shunt vessels were identical. The ratio of the peak flow velocity measured at the aortic and the pulmonary ends of the shunt vessel was significantly larger in the segmentally stenosed shunt vessels than in the uniformly patent shunt vessels (p < 0.001). The ratio in the two shunt vessels only partially imaged by cross sectional echocardiography indicated that they were segmentally stenosed. The combination of cross sectional and Doppler echocardiography may be useful for determining either the patency or the morphology of an aortopulmonary shunt.


Morphological study of defects of the atrial septum within the oval fossa: implications for transcatheter closure of left-to-right shunt.

To determine the anatomical variability of the oval fossa in cases of atrial septal defect and to find out which factors might make such defects suitable or unsuitable for closure by umbrella or clamshell devices. 100 specimens with defects of the atrial septum within the oval fossa were studied, especially the position of the defects within the fossa; the area of the defect in relation to the total area of the oval fossa; the shape of the rims and flap valve of the oval fossa; and the anatomical variability in the eustachian and thebesian valves. The oval fossa was displaced to the mouth of the inferior caval vein in four cases; displaced to the mouth of superior caval vein in two cases; placed on the middle of the interatrial wall in 43; or placed slightly towards the inferior caval vein in 51. Because of their shape 29 of the hearts were considered to be unsuitable for transcatheter closure of the defect. This was because the defect was too large (16 hearts); the oval fossa was displaced to the mouth of the inferior caval vein (four hearts) or to the superior caval vein (two hearts); lacked its anterior rim (two hearts); lacked the posteroinferior rim (one heart); because a thick eustachian valve was displaced posteriorly forming a false posteroinferior rim (one heart); or because the strand of insertion of the floor of the oval fossa was too distant from the left atrial aspect (three hearts). 68 hearts appeared to be ideal candidates for transcatheter closure; 3 would probably have been suitable; but 29 were unsuitable. These morphological variations might explain why the procedure has been unsuccessful in so many cases. Patients should be screened before any attempt is made at transcatheter closure.


Severe haemolysis after transcatheter duct occlusion: a non-surgical remedy.

Severe mechanical haemolysis occurred in a seven month old infant after the insertion of a 17 mm Rashkind double umbrella device. The placement of a second device 23 days after the initial procedure abolished haemolysis.


Spontaneously acquired fistula from the right coronary artery to the right ventricular cavity.

A 47 year old man developed a fistula from the right ventricular branch of the right coronary artery to the right ventricular cavity in association with distal occlusion of the main trunk of the right coronary artery. There was no clinical or electrocardiographic evidence of acute myocardial infarction.


Mortality within hospital after resuscitation from ventricular fibrillation outside hospital.

To determine factors related to mortality within hospital after successful resuscitation from ventricular fibrillation outside hospital by a mobile coronary care unit manned by a physician. Retrospective review of records of patients resuscitated and admitted to hospital between 1 January 1966 and 31 December 1987. Mobile coronary care unit, coronary care unit, and cardiology department. 281 patients (227 male), aged 14-82 (mean 58) successfully resuscitated from ventricular fibrillation outside hospital of whom 182 (65%) developed ventricular fibrillation before the arrival of the mobile coronary care unit. The aetiology of ventricular fibrillation was acute myocardial infarction in 194 patients (69%), ischaemic heart disease without infarction in 71 (25%), and other or unknown in 16 (6%). Death within hospital. There were 91 deaths in hospital (32%). Factors on univariate analysis significantly associated with increased mortality were patient age > or = 60 years, previous myocardial infarction or cerebrovascular disease, prior digoxin or diuretic treatment, collapse without prior chest pain or with pain lasting 30 minutes or less, defibrillation delayed by > or = 5 min, > or = four shocks required to correct ventricular fibrillation, left ventricular failure or pulmonary oedema and cardiogenic shock after successful defibrillation, and coma on admission to hospital. On multivariate analysis the most important factors (in rank order) were cardiogenic shock after defibrillation, coma on admission to hospital, age > or = 60 years and the requirement for four or more shocks to correct ventricular fibrillation. The in-hospital mortality of patients resuscitated from ventricular fibrillation outside hospital was related to patient characteristics before the cardiac arrest and to the immediate haemodynamic and neurological status after correction of ventricular fibrillation as well as to factors at the resuscitation itself. The in-hospital mortality of this study compares favourably with the results obtained by units staffed by paramedical workers and emergency medical technicians, although 35% (99/281) of the patients had ventricular fibrillation after the arrival of the mobile unit and defibrillation was thus rapid.


Insulin resistance, diabetes, and risk markers for ischaemic heart disease in Asian men and non-Asian in Bradford.

To examine the hypothesis, in a community not studied before, that insulin resistance associated with centralised adiposity is the mechanism underlying the predisposition of Asian immigrant communities to both ischaemic heart disease and diabetes mellitus. Cross sectional study within one socioeconomic stratum. Two factories in the textile sector in Bradford, West Yorkshire. Male manual workers of Asian (110) and non-Asian origin (156) aged 20-65 years. Diabetes was almost three times more prevalent in the Asian group. Two hours after an oral glucose load Asian men had double the serum insulin concentrations of non-Asian men (p < 0.0001). Asian men also had significantly lower concentrations of plasma total cholesterol (p < 0.03), high density lipoprotein cholesterol (HDL) (HDL2, p < 0.0001; HDL3, p < 0.0001), and apolipoprotein AI (p < 0.0001). Fasting plasma triglyceride concentrations were slightly higher (p = 0.072) in the Asian men; thus the ratio of triglyceride cholesterol was higher (p = 0.006). The inter-relation between serum insulin and plasma lipid concentrations indicated metabolic differences between the ethnic groups. Insulin concentrations were associated with cholesterol concentrations in the Asian men only and there was a lack of association between triglyceride, low density lipoprotein cholesterol, and HDL cholesterol in this group. The risk marker profile in the Asian men was therefore quite different to that of their non-Asian counterparts and was associated with a greater tendency to centralised adiposity. These data support the insulin resistance hypothesis and thus have important implications for strategies for the prevention of heart disease in Asian communities in the United Kingdom.


Strenuous exercise, plasma fibrinogen, and factor VII activity.

To assess the effect of physical activity on plasma fibrinogen and factor VII activity and thus on the risk of ischaemic heart disease. Cross sectional survey. Ten group practices in the Medical Research Council's General Practice Research Framework. 3967 men aged 45-69 attending screening clinics for the thrombosis prevention trial. Structured interview to elicit the intensity and frequency of physical exercise during past month. Measurement of fibrinogen, factor VII activity, cholesterol concentration, blood pressure, and other indices of ischaemic heart disease risk. Strenuous exercise was associated with significantly lower fibrinogen concentrations than mild exercise, implying a difference of about 15% in the risk of ischaemic heart disease. Strenuous exercise was also associated with lower cholesterol concentrations. More frequent strenuous exercise was associated with lower factor VII activity. With the recognition of plasma fibrinogen as a strong index of ischaemic heart disease risk the results of this and other studies suggest a pathway through which the protective effect of strenuous exercise may partly be mediated and they provide doctors and patients with a valuable incentive towards prevention, particularly in those whose risk of ischaemic heart disease is substantially due to raised fibrinogen concentrations.


Comparative electrophysiological effects of captopril or hydralazine combined with nitrate in patients with left ventricular dysfunction and inducible ventricular tachycardia.

To assess the electrophysiological and antiarrhythmic effects of pharmacological load manipulation by an angiotensin converting enzyme (ACE) inhibitor (captopril) and a direct vasodilator (hydralazine plus isosorbide mononitrate) in patients with inducible ventricular tachycardia and impaired left ventricular function. Randomised open label cross-over comparison of three regimens. Tertiary arrhythmia referral centre. Eight patients with reduced left ventricular function and sustained ventricular tachycardia inducible by programmed stimulation. Three treatment regimens each of 48 hours duration: captopril, hydralazine plus isosorbide mononitrate, and control (no vasodilator). Changes in central haemodynamics, electrophysiological parameters, and induction of ventricular tachycardia during treatment with captopril, or hydralazine combined with nitrate, compared with a control period. Both vasodilator treatments produced similar balanced reductions in peak systolic pressures and filling pressures compared with controls. Captopril had no effect on sinus cycle length, atrial refractoriness, or intraventricular conduction, but prolonged ventricular effective and functional refractory periods and QT interval during constant rate atrial pacing. Hydralazine combined with nitrate did not significantly alter any electrophysiological variable. Ventricular tachycardia was similarly inducible during all three periods. Load manipulation by captopril but not hydralazine combined with nitrate prolonged ventricular refractoriness and repolarisation, possibly reflecting a combination of mechano-electrical effect with the restraining influence of ACE inhibitors on reflex sympathetic stimulation.


Role of atrial contraction and synchrony of ventricular contraction in the optimisation of ventriculoarterial coupling in humans.

To examine the effects of pacing modes on the interaction between the left ventricle and arterial system in humans. The slope of the end systolic pressure-volume relation (end systolic elastance), effective arterial elastance, the ratio of effective arterial elastance to end systolic elastance, and mechanical energy efficiency were compared under different pacing modes (atrial, atrioventricular, and ventricular). Nine male patients with sick sinus syndrome who had cardiac catheterisation for diagnosis and to see whether they needed a pacemaker. A conductance catheter with tip-manometer was inserted into the left ventricle to obtain pressure-volume loops, and two pacing catheters were inserted into the right atrium and into the right ventricle respectively. End systolic elastance was lower in atrioventricular pacing than in atrial pacing, but effective arterial elastance was not significantly different. End systolic elastance was lower in ventricular pacing than in atrioventricular pacing, and effective arterial elastance was higher in ventricular pacing than in atrioventricular pacing. Consequently the ratio of effective arterial elastance to end systolic elastance was lowest in atrial pacing and highest in ventricular pacing, and mechanical energy efficiency was highest in atrial pacing and lowest in ventricular pacing. Atrial contraction and synchronous ventricular contraction independently optimise ventriculoarterial coupling in terms of a transfer of energy. Thus atrial pacing gives the best ventriculo-arterial coupling among these pacing modes.


Changes in myocardial echo amplitude during reversible ischaemia in humans.

This study investigated the changes in regional myocardial ultrasonic backscatter, measured as myocardial echo amplitude, that occur during reversible myocardial ischaemia in humans. Left anterior descending coronary angioplasty was used to produce reversible myocardial ischaemia in human subjects. Regional myocardial echo amplitude was studied in the interventricular septum and left ventricular posterior free wall before, during, and after coronary occlusion with the angioplasty balloon. Wall motion analysis of the left ventricle was performed from simultaneous cross sectional echocardiographic imaging. Patients were studied prospectively. Six patients (mean age 56 (SD 11), range 46 to 69 years) with single vessel, left anterior descending coronary artery stenoses, were investigated during elective coronary angioplasty. A total of 11 balloon inflations were studied. All patient studies were performed at Harefield Hospital. Echo amplitude analysis was performed at the Royal Brompton Hospital. Angioplasty was performed by the usual procedure at Harefield Hospital for elective coronary angioplasty. All routine medication including beta blockers and calcium antagonists were continued. Inflation pressures were up to 12 atm (1212 kPa) and mean inflation time ranged from 30 to 120 (86 (31)) s. In four studies the first inflation was examined, in three the second, in two the third, and in one each the fourth and fifth inflations. Echo amplitude and cross sectional echo-cardiographic studies were recorded with a 3.5 MHz Advanced Technology Laboratories (ATL) (720A/8736 series) mechanical sector scanner and an ATL Mark III (860-1 series) echocardiograph system with 45 dB logarithmic grey scale compression. Regional echo amplitude was examined in four regions of the left ventricle--namely, the basal and mid-septum, and basal and mid-posterior wall. Consecutive end diastolic and end systolic frames were analysed and cyclic variation was determined as the difference between the level of echo amplitude at end diastole and at end systole. Measurements were made before balloon inflation, at peak inflation, and after balloon deflation. Regional wall motion and systolic wall thickening were analysed qualitatively. Before balloon inflation, cyclic variation in echo amplitude was noted in all regions (basal septum, 2.4 (SD 1.1) dB; mid-septum, 2.5 (1.1) dB; basal posterior wall, 3.3 (2.1) dB; mid-posterior wall, 3.9 (1.6) dB). During balloon inflation there was a significant fall in cyclic variation to 0.4 (0.9) dB (p < 0.0002) in the mid-septum. This was predominantly owing to an increase in end systolic echo amplitude from 5.4 (2.0) dB to 9.3 (1.9) dB (p < or = 0.01). This was associated with the development of severe hypokinesis or akinesis in the mid-septum. No significant changes in echo amplitude occurred in the three other regions examined. Changes were completely reversed after balloon deflation. These results suggest a causal relation between occlusion of the supplying coronary artery and blunting of myocardial echo amplitude cyclic variation. It is suggested that balloon occlusion produced myocardial ischaemia. The resultant impairment of myocardial contraction then caused a blunting of cyclic variation in echo amplitude. The results of this study provide further data about the ability of quantitative studies of ultrasonic backscatter to identify alterations in the myocardium during injury.


Symptomatic and silent myocardial ischaemia in hypertensive patients with left ventricular hypertrophy.

To assess the prevalence of symptomatic and silent myocardial ischaemia in patients with hypertensive left ventricular hypertrophy. Cross sectional study. University department of medical cardiology. 90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with left ventricular hypertrophy due to essential hypertension. 48 hour ambulatory ST segment monitoring (all patients), exercise electrocardiography (n = 79), stress thallium scintigraphy (n = 80), coronary arteriography (n = 35). 43 patients had at least one episode of ST segment depression on ambulatory electrocardiographic monitoring. The median number of episodes was 16 (range 1 to 84) with a median duration of 8.6 (range 2 to 17) min. Over 90% of these episodes were clinically silent. 26 patients had positive exercise electrocardiography and 48 patients had reversible thallium perfusion defects despite chest pain during exercise in only five patients. 18 of the 35 patients who had coronary arteriography had important coronary artery disease. Seven of these patients gave no history of chest pain. Symptomatic and silent myocardial ischaemia are common in hypertensive patients with left ventricular hypertrophy, even in the absence of epicardial coronary artery disease.


Circulating endothelin in acute ischaemic syndromes.

Endothelin is an extremely potent vasoconstrictor that may have a role in the pathogenesis of acute myocardial ischaemia. Atrial natriuretic factor is an endogenous antagonist of endothelin. To find the pattern and possible importance of circulating endothelin in ischaemic heart disease, concentrations in normal controls and those in patients with stable and unstable angina, acute myocardial infarction, and chronic cardiac failure were compared. The relation between circulating concentrations of endothelin and atrial natriuretic factor in the aftermath of myocardial infarction was also examined. Eighteen patients with acute myocardial infarction, 10 with unstable angina, 10 with stable angina, 12 with chronic cardiac failure, and 10 normal controls were studied. Endothelin concentration was measured in venous plasma by radioimmunoassay. In patients with acute myocardial infarction simultaneous concentrations of endothelin and atrial natriuretic factor were measured on admission and at one, four, and 24 hours. Mean concentrations (SEM) of endothelin were 5.72 (0.19) fmol/ml in controls, 6.56 (0.48) fmol/ml in stable angina, 6.41 (0.48) fmol/ml in unstable angina, and 13.83 (0.95) fmol/ml in chronic cardiac failure. In acute myocardial infarction concentrations were 8.81 (0.69) fmol/ml on admission, 11.85 (1.02) fmol/ml at one hour, 11.88 (1.10) fmol/ml at four hours, and 7.30 (0.49) fmol/ml at 24 hours. Concentrations of atrial natriuretic factor at the same times were 68.1 (13.1) pg/ml, 8.4 (1.5) pg/ml, 24.4 (4.1) pg/ml, and 42.0 (6.9) pg/ml. Plasma endothelin is raised in chronic heart failure and in the aftermath of acute myocardial infarction but not in stable or unstable angina. After myocardial infarction endothelin concentrations are raised whereas concentrations of atrial natriuretic factor are relatively low. The role of endothelin in the pathogenesis of acute myocardial infarction and its interactions with other humoral factors require further investigation.


Emergency coronary artery surgery after refractory cardiac arrest: a single centre experience.

To determine the incidence and outcome of refractory cardiac arrest necessitating emergency coronary artery bypass grafting. Retrospective survey of cardiac catheterisation and surgical records. The London Chest Hospital. All patients requiring emergency coronary artery bypass grafting after cardiovascular collapse in the catheterisation suite between January 1984 and December 1989. Incidence of refractory cardiac arrest in the study group and perioperative mortality. Thirteen of 8675 patients undergoing coronary arteriography or angioplasty had refractory cardiac arrests. Five patients died, but the remainder survived to be discharged from hospital without serious morbidity. Without immediate surgical intervention the mortality for these 13 patients would have been 100%.


Predictors of risk in patients with unstable angina admitted to a district general hospital.

To observe the long-term prognosis of patients with unstable angina and select simple criteria to identify high and low risk subgroups. A six month prospective survey with three year follow up. One eleven bed coronary care unit. All patients admitted with chest pain in whom no infarct was confirmed by subsequent electrocardiographic or enzyme changes and for whom no alternative cause of chest pain was found were studied. Unstable angina was also diagnosed if there was evidence of myocardial ischaemia in the form of previous effort angina, previous myocardial infarction, or if transient electrocardiographic changes accompanied the pain. When none of the above were present, chest pain without a known cause, was diagnosed. No routine intervention. Angiography and revascularisation for persistent symptoms despite medical treatment. Death or non-fatal infarction. In the 141 patients with unstable angina there were eight deaths and five non-fatal infarctions during the first eight weeks. Symptoms of increasing angina before admission were similar in all three groups and did not help predict early complications. Recurrence of pain in hospital, a rise in cardiac enzymes to less than twice the upper limit of normal, and transient electrocardiographic changes were all associated with an increased risk of early events. The presence of either abnormal enzyme activity or more than five episodes of pain in hospital identified a group of 49 in whom 11 of the 13 early events occurred. After three years, 29 of the 141 patients had died and eight had had infarctions (overall event rate 26%). Seventeen had undergone revascularisation (12%) and 51 (36%) were on antianginal treatment. Thirty six (26%) were still alive, without new myocardial infarction, and were free of angina. In the 29 patients with chest pain without a known cause there were no early events and only one non-fatal infarction during the three year follow up. When patients are admitted to the coronary care unit with chest pain not due to myocardial infarction, the history, electrocardiography and measurement of cardiac enzymes are sufficient to identify high and low risk subgroups.


Atrial myxoma: tumour or trauma?

A mass lesion developed in the right atrium at the site of a trans-septal puncture after percutaneous balloon dilatation of the mitral valve in a man aged 74. The lesion had the pathological appearance of an atrial myxoma and seemed to have developed after trauma to the intra-atrial septum. This case suggests that at least some atrial myxomas are reactive rather than neoplastic in origin.


Endocarditis with aneurysm involving an aortic homograft used to correct a truncus arteriosus: medical-surgical salvage.

An aneurysm of an aortic homograft conduit, used to correct a type I truncus arteriosus anomaly in a four month old infant, developed when the patient was 15. Blood cultures grew Staphylococcus aureus. The aneurysm was detected by magnetic resonance imaging and digital subtraction angiocardiography. An emergency open heart operation, guided by these investigations, was performed to remove the original homograft and replace it with another valved aortic homograft. Postoperative antibiotic treatment had to be stopped when profound neutropenia developed. This responded to treatment with recombinant human granulocyte colony stimulating factor. Three years later she was symptom free and did not require medication. Chest x rays and echocardiograms showed a normally functioning heart and conduit valve.


Monitoring of streptokinase resistance titre in acute myocardial infarction patients up to 30 months after giving streptokinase or anistreplase and related studies to measure specific antistreptokinase IgG.

To examine the induction of antistreptokinase antibodies after giving streptokinase or anistreplase to patients with acute myocardial infarction. Patients were randomly allocated to receive either 1.5 x 10(6) IU, streptokinase or 30U anistreplase in a double blind study. Blood samples were collected immediately before treatment and subsequently at intervals up to 30 months; plasma samples were assayed for streptokinase resistance titre (functional assay) and streptokinase binding by IgG (microradioimmunoassay). Cardiology department in a general hospital. 128 consecutive eligible patients. Samples were collected for up to one year according to a prospective design: a subsection of 47 patients was selected for intensive study over the first 14 days. After one year, all available patients (67) were sampled on one further occasion. Antibody responses to streptokinase and anistreplase were similar. Streptokinase resistance titres exceeded pretreatment concentrations five days after dosing, and values peaked at 14 days. By 12 months after dosing, 92% of resistance titres (n = 84) had returned to within the pretreatment range. Antistreptokinase IgG concentrations also exceeded baseline concentrations within five days and peaked at 14 days. Half of the individual values had returned to within the pretreatment range by 12 months (n = 84) and 89% by 30 months (n = 18). Although we cannot be sure of the clinical significance, because of the increased likelihood of resistance due to antistreptokinase antibody, streptokinase and anistreplase may not be effective if administered more than five days after an earlier dose of streptokinase or anistreplase, particularly between five days and 12 months, and increased antistreptokinase antibody may increase the risk of allergic-type reactions.


Streptokinase induced defibrination assessed by thrombin time: effects on residual coronary stenosis and left ventricular ejection fraction.

To evaluate laboratory markers of defibrination early after thrombolytic therapy and to determine their relation to residual stenosis and left ventricular ejection fraction measured angiographically before discharge from hospital. Prospective analysis of defibrination after streptokinase measured by fibrinogen assay and thrombin time to provide a comparison of these coagulation variables for predicting angiographic responses to treatment in patients with acute myocardial infarction. The coronary care unit of a district general hospital. 44 patients with acute myocardial infarction treated by streptokinase infusion, all of whom underwent paired blood sampling before and one hour after streptokinase and cardiac catheterisation at a median of six (interquartile range 3-9) days later. Assay of thrombin time and plasma fibrinogen concentrations one hour after streptokinase infusion. Relations between these coagulation variables and residual stenosis in the infarct related coronary artery and left ventricular ejection fraction. Separate analyses are presented for all patients (n = 44) and those with patency of the infarct related artery (n = 35). Streptokinase infusion produced profound defibrination in every patient as shown by changes in thrombin time and circulating fibrinogen. Thrombin time after streptokinase infusion correlated significantly with both residual stenosis (r = -0.43, p < 0.005) and left ventricular ejection fraction (r = 0.38, p < 0.02). The importance of these correlations was emphasised by the interquartile group comparison which showed that a thrombin time > or = 49 seconds predicted a residual stenosis of 74% and an ejection fraction of 65%, compared with 90% and 49% for a thrombin time < or = 31 seconds (p < 0.01). When the analysis was restricted to patients with patency of the infarct related artery, the correlation between thrombin time and residual stenosis remained significant and group comparisons continued to show that patients in the highest quartile range had more widely patent arteries and better preservation of ejection fraction. Analysis of the fibrinogen data, on the other hand, showed insignificant or only marginally significant correlations with these angiographic variables. Early after streptokinase infusion for acute myocardial infarction, the level of defibrination measured by thrombin time has an important influence on residual coronary stenosis and left ventricular ejection fraction at discharge from hospital, values above 49 seconds being associated with the best angiographic result.


Early and long term results of re-operation for coronary artery disease.

To define the incidence, possible causes, operative procedure, and early and medium term results of patients undergoing reoperation for coronary artery disease. A retrospective analysis of patients undergoing reoperation in one hospital during a 10 year period. A regional cardiothoracic centre. 115 patients had reoperation for recurrent angina, 1-17 years (mean (SD) 7.4 (3.9)) after primary revascularisation. They received 279 grafts (2.4 grafts per patient); 58% of the grafts were anasatomosed to previously grafted vessels. The internal mammary artery was used in 87% of patients who required grafts to the left anterior descending coronary artery. Reoperation accounted for 8.3% of the total number of patients who underwent coronary bypass grafting. Graft failure alone or in combination with other factors was judged to be the cause of recurrence of symptoms in 87%. 42% of patients had two or more coronary risk factors. The early mortality was 5.2% and the actuarial survival at five and 10 years was 90.4% and 88.4% respectively. 85% of the survivors had initial complete relief of angina and 14% had partial improvement. Freedom from recurrent symptoms at five and 10 years was 66.6% and 34.6% respectively. Vein graft failure either alone or in combination with progression of native coronary disease is the main cause for symptomatic deterioration after bypass grafting. Reoperation can be performed with slightly increased risk and can give good early and medium term results.


Influence of power and aerobic exercise training on haemostatic factors after coronary artery surgery.

To determine the effects of aerobic and power exercise training on haemostatic factors after coronary artery surgery and to compare the effect of the two exercise programmes. A prospective randomised controlled study of six months aerobic and power exercise training in men after coronary artery surgery. Exercise rehabilitation classes in a teaching hospital in Glasgow. 55 men within 12 months of coronary artery surgery recruited from surgical centres and medical clinics and asked to participate in the study. Assessments, including a treadmill test, measurements of haemoglobin, platelet, fibrinogen, factor VIIc, and fibrinopeptide A concentrations, and packed cell volume, done at baseline, three months, and six months. Patients in the two exercise groups attended training sessions three times weekly for six months. Control patients had no formal exercise training but continued with their leisure time activities. Exercise performance on a treadmill, haematology, and haemostatic factor assays at baseline, three months, and six months. In the aerobic trained group exercise performance increased significantly over baseline at three months (interval change 146.7, 95% confidence interval (95% CI) 52.5 to 240.9 s, p = 0.003) and was maintained at six months (interval change 172.1, 95% CI 63.3 to 280.9 s, p = 0.002). In the power trained groups significant improvement in exercise performance was delayed until six months (interval change 99.9 s, 95% CI 20.3 to 170.5 s, p = 0.01). Exercise performance in the control did not change significantly. Haemoglobin, concentration, packed cell volume, and platelet counts did not change significantly at any time. Fibrinogen concentration was significantly lower in the aerobic group than the other two groups at three months (2.96 g/dl compared with 3.3 g/dl and 3.87 g/dl in the power and control groups, p = 0.01). The power group had a lower fibrinogen concentration than the control group (p = 0.04). The lower fibrinogen concentration in the aerobic group was maintained at six months. There was a gradual rise in factor VIIc concentrations in the aerobic and control groups compared with a small fall in the power group. Fibrinopeptide A concentrations showed no consistent changes. Aerobic exercise training after coronary artery surgery causes an early favourable change in treadmill performance and in fibrinogen concentrations, that is maintained with further training. Power exercise training causes delayed benefit in treadmill performance. It also causes a small fall in fibrinogen concentrations. These changes may be relevant in reducing cardiovascular morbidity from graft failure and occurrence of myocardial infarction after coronary artery surgery.


Jugular venous 'a' wave in pulmonary hypertension: new insights from a Doppler echocardiographic study.

To study the mechanisms underlying the dominant 'a' wave seen in patients with primary pulmonary hypertension. Retrospective and prospective examination of the jugular venous pulse recording, flow in the superior vena cava, and Doppler echocardiographic studies. A tertiary referral centre for both cardiac and pulmonary disease, with facilities for invasive and non-invasive investigation, and assessment for heart and heart-lung transplantation. 12 patients with primary pulmonary hypertension, most being considered for heart-lung transplantation. Two distinct patterns of venous pulse and superior vena caval flow were identified: a dominant 'a' wave with no 'v' wave, an absent or poorly developed 'y' descent, and exclusively systolic downward flow in the superior vena cava (group 1, n = 8), and a dominant 'v' wave, deep 'y' descent and exclusively diastolic downward flow in the superior vena cava (group 2, n = 4). A comparison between the two groups showed age (mean (SD)) 42 (18) v 36 (7) years, RR interval 700 (65) v 740 (240) ms, left ventricular end diastolic dimension 3.6 (0.8) v 3.2 (1.0) cm and end systolic dimension 2.1 (0.5) v 2.3 (0.3) cm, right ventricular end diastolic dimension 2.6 (0.5) v 2.8 (0.6) cm, and pressure drop between right ventricle and right atrium 60 (8) v 70 (34) mm Hg to be similar. Duration of tricuspid regurgitation 520 (30) v 420 (130) ms and the time interval of pulmonary closure to the end of the tricuspid regurgitant signal 140 (30) v 110 (40) ms were longer in group 1 compared with group 2, whereas right ventricular filling time was much shorter 180 (70) v 350 (130) ms. In seven patients from group 1, a single peak of forward tricuspid flow was present, but this pattern was seen in only one patient from group 2. In patients with primary pulmonary hypertension, the apparent 'a' wave seen in the venous pulse is, in fact, a summation wave. It is probably the result of large pressure changes that must underlie rapid acceleration and deceleration of blood across the tricuspid valve when the right ventricular filling time is short.


Continuous wave Doppler echocardiography after surgical repair of coarctation of the aorta.

To find how closely pressure gradients across the aortic arch derived from Doppler echocardiography reflect gradients measured by catheter after surgical repair of coarctation of the aorta. Pressure drop across the aortic arch was measured simultaneously by continuous wave Doppler and double lumen catheter in 20 patients with repaired coarctation of the aorta. The peak pressure drop estimated by Doppler was almost invariably higher than the peak to peak gradient measured by catheter, as might be expected. Wide variation was seen between the Doppler measured pressure drop and instantaneous peak gradient measured by catheter, ranging from +22 to -17 mm Hg. The reasons for these differences are unclear but are probably related to a combination of complex flow dynamics in the aortic arch, difficulty in closely aligning the Doppler beam with flow, and inability to measure flow velocity immediately proximal to the site of the surgical repair with continuous wave Doppler. Continuous wave Doppler echocardiography may significantly overestimate or underestimate the pressure drop after repair of coarctation and it should be interpreted with caution in individual patients. Catheterisation with angiography remains the reference standard for assessment of surgical repair of the aortic arch.


Optimal pacing modes after cardiac transplantation: is synchronisation of recipient and donor atria beneficial?

To investigate the response of the transplanted heart to different pacing modes and to synchronisation of the recipient and donor atria in terms of cardiac output at rest. Doppler derived cardiac output measurements at three pacing rates (90/min, 110/min and 130/min) in five pacing modes: right ventricular pacing, donor atrial pacing, recipient-donor synchronous pacing, donor atrial-ventricular sequential pacing, and synchronous recipient-donor atrial-ventricular sequential pacing. 11 healthy cardiac transplant recipients with three pairs of epicardial leads inserted at transplantation. Donor atrial pacing (+11% overall) and donor atrial-ventricular sequential pacing (+8% overall) were significantly better than right ventricular pacing (p < 0.001) at all pacing rates. Synchronised pacing of recipient and donor atrial segments did not confer additional benefit in either atrial or atrial-ventricular sequential modes of pacing in terms of cardiac output at rest at these fixed rates. Atrial pacing or atrial-ventricular sequential pacing appear to be appropriate modes in cardiac transplant recipients. Synchronisation of recipient and donor atrial segments in this study produced no additional benefit. Chronotropic competence in these patients may, however, result in improved exercise capacity and deserves further investigation.


Arrhythmias after the Fontan procedure.

To study the determinants and outcome of arrhythmias after the Fontan type operation. Retrospective analysis of data in patients operated on between 1972 and 1986 (follow up 5-19 years (mean 12 years)). All 60 patients undergoing a Fontan type procedure at the National Heart Hospital, London, during the study period (mean age (SD) 12.3 (6.8) years). Postoperative arrhythmias occurred in 34 patients (57%), and 11 (58%) of 19 early postoperative deaths (within seven days) were related to arrhythmias. Early arrhythmias occurred in 19 (32%) patients of whom 11 (58%) died. All patients with early atrial fibrillation and His bundle tachycardia died and only preoperative atrial fibrillation recurred early. There was a higher incidence of early arrhythmias, which were less well tolerated, in double inlet single ventricle patients (9/19) than in those with tricuspid atresia (8/37). There were no other preoperative determinants of early arrhythmias or deaths from early arrhythmia. Late (after seven days) arrhythmias occurred in 15 (37% of hospital survivors). They had higher right atrial (RA) pressures both early and late after operation and had lower ventricular ejection fractions late after operation. Of those with atrial arrhythmias 86% had RA obstruction and 57% had an RA thrombus or pulmonary embolism at presentation; this was also confirmed in two patients in whom late sudden deaths occurred. Atrial fibrillation early after reoperation for RA obstruction was fatal. The actuarial arrhythmia free survival for hospital survivors was 60% at 10 years. Early postoperative arrhythmias were poorly tolerated, particularly atrial fibrillation and His bundle tachycardia. Previous atrial fibrillation was a relative contraindication to this procedure. Late postoperative arrhythmias were associated with higher RA pressures measured both early and late after operation and worse late ventricular function. Late arrhythmias may be the first manifestation of RA obstruction, which must be sought. RA thrombus was common in patients with atrial arrhythmias and should be treated early with anticoagulants.


Repeatability of measurements and sources of variability in tests of cardiovascular autonomic function.

To determine the repeatability and sources of variability of clinical tests of cardiovascular autonomic function. The commonly used electrocardiographic related tests of autonomic function were studied. Two repeat measurements of all tests were made on all subjects on four separate days over a four week period. Ten normal subjects with no known autonomic dysfunction were investigated. These were deep breathing (subject seated and supine), Valsalva manoeuvre, standing up from lying position, and normal relaxed breathing (subject supine). During the tests the electrocardiogram and respiratory pattern were recorded by computer. Beat to beat RR intervals were measured automatically from the electrocardiogram, and from these the results of the tests were calculated. Variance analysis showed significant between subject variability for all tests (p < 0.005), but some tests showed a much smaller relative within subject variability than others. Average repeatability data (within subject SD) for each test were calculated, and included deep breathing sitting (max-min) RR (46 ms), Valsalva ratio (0.17), and lying to standing RR ratio (0.11). These compare with between subject SDs of 65 ms, 0.38, and 0.13 respectively, at mean values of 305 ms, 1.92, and 1.15 respectively. The data highlighted one subject with the poorest repeatability, whose electrocardiogram turned out on closer inspection to be under atrial rather than sinus control at times. Poor repeatability in the other subjects was related to variability in the respiratory pattern, and in the deep breathing test, repeat variability was significantly correlated (r = 0.79) with variability in the respiratory amplitude (p < 0.05). Repeatability data should be available to each laboratory carrying out autonomic function tests. The data provided in this study could be used as a baseline. Poor repeatability highlights the need to re-examine the test procedures, or the test data from specific subjects. Variability of respiratory pattern is associated with poor repeatability, and so careful instructions on respiration should be given to each subject before the tests.


Raised international normalised ratio (INR): is it a cause or an effect of late cardiac tamponade?

Two cases of late cardiac tamponade after valve replacement surgery are reported: both patients were treated with oral anticoagulants (warfarin) after operation. An erratic response in the international normalised ratio (INR) was found before the diagnosis of late tamponade. It is suggested that this response of the INR may be an early indicator of late cardiac tamponade rather than a cause.


Rare variant of truncus arteriosus with intact ventricular septum and hypoplastic right ventricle.

A three week old girl was admitted to hospital with severe congestive heart failure and cyanosis. Cross sectional and Doppler echocardiography and cardiac catheterisation showed a unique variant of truncus arteriosus with an intact ventricular septum. The trunk rose only from the left ventricle and was associated with a hypoplastic right ventricle with sinusoids to the right coronary artery.


Unmasking of a second atrioventricular accessory connection by adenosine in a child with a long RP' reentrant tachycardia.

A second unidirectional, retrograde accessory atrioventricular pathway was unmasked by adenosine during the intracardiac evaluation of a child with a reentrant long RP' tachycardia. This case is further evidence of the value of adenosine during the evaluation of these types of tachycardias.


Propionibacterium acnes causing an aortic root abscess.

A case of endocarditis caused by Propionibacterium acnes associated with an aortic root abscess is presented. This supports the current opinion that aortic root abscesses are not necessarily associated with microorganisms of high virulence.