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7789030
Case report: symptomatic metastasis from a sacrococcygeal chordoma.
Chordoma is generally thought to be a locally invasive tumour of low metastatic potential. Review of the literature suggests that metastatic spread from chordoma is not an uncommon occurrence, but that the metastases are usually clinically silent. We present an unusual case where a metastasis from a sacrococcygeal chordoma produced a syndrome of lumbar root compression after resection of the primary lesion.
7789031
Case report: calcified stones in right-sided colonic diverticula stimulating gallstones.
Right-sided colonic diverticulosis, though unusual in the Western population, is common in the Orient. Calcified stones are rarely found within colonic diverticula. Standard textbooks of diagnostic radiology do not list calcified stones within caecal or ascending colonic diverticula as possible causes of calcification in the right hypochondrium or right iliac fossa. We present a patient with multiple laminated right-sided diverticular concretions mimicking gallstones. This possibility should be included in the differential diagnosis of gallstones or calcifications on the right side of the abdomen.
7789029
Case report: multiple epidermoid cysts of the testes--the ultrasound appearances.
Epidermoid cysts are uncommon tumours of the testes representing approximately 1% of all testicular tumours. Their importance lies in the fact that they are completely benign and can be treated by local excision, thereby saving the patient an orchidectomy. We describe a case in which the patient had multiple epidermoid cysts involving both testes and faced possible bilateral orchidectomy.
7789027
Amyloid goitre: CT and MR findings.
Two cases of amyloid goitre presented as an enlarged thyroid mass with cystic components. Solid parts of the goitre showed high attenuation on computed tomography (CT) and moderate hypointensity on T1 and T2-weighted images. Fine needle aspiration was negative for amyloid, but pathological studies of surgical specimens demonstrated amyloid infiltration of the thyroid interstitium and regressive colloid cysts. In a patient at risk for systemic amyloidosis, thyroid enlargement with a cystic component suggests amyloid goitre. In this case, needle biopsies should be directed to solid areas of the mass because amyloid material may not be present in the cysts.
7789028
Laryngeal chondroma: an unusual cause of upper airway obstruction.
Cartilaginous tumours of the larynx should be considered in the differential diagnosis of upper airway obstruction. We report two cases of chondroma of the thyroid cartilage and discuss the radiological findings in each case.
7789026
Demonstration of popliteal artery entrapment on leg muscle scintigraphy with 99mTc MIBI and single photon emission tomography.
Popliteal artery entrapment is difficult to diagnose even at surgery. Early diagnosis is important as the prognosis is better if detected before the onset of complications. There is no sensitive method for the evaluation of this condition. We describe three cases detected by a new technique using 99mTc methoxy isobutyl isonitrile (MIBI) with single photon emission tomography. The scintigraphic features of entrapment and the advantage of MIBI leg scintigraphy over other methods are discussed.
7789025
V/Q defects and deep venous thrombosis following total hip replacement.
Seventy-two patients undergoing elective total hip replacement were studied with bilateral venography, pre-operative and post-operative lung scans. Twelve belonged to a control group that received placebo injections and 60 patients to treatment groups that received low molecular weight heparin. The incidence of deep venous thrombosis was 11 (92%) of 12 patients in the control group and 18 (30%) of 60 patients in the treatment group (X2: P < 0.001). The incidence of pulmonary embolism (new unmatched perfusion defects) was five (42%) of the 12 patients in the control group and five (8.3%) of the 60 patients in the treatment groups (X2: P < 0.002). The incidence of pulmonary embolism (new unmatched perfusion defects) was eight (27.5%) of 29 patients with deep venous thrombosis and two (4.6%) of 43 without deep venous thrombosis (X2: P < 0.02). Of the ten patients who had pulmonary embolism according to this study's criteria (one or more new defect on perfusion, unmatched on the ventilation scan), eight would have been classified as high probability by the Biello criteria, and only five by the PIOPED criteria, if the pre-operative scans were not available. We conclude that having a pre-operative lung scan improves ability to interpret the postoperative lung scans in high risk patients.
7789024
The prevalence and clinical significance of lymphadenopathy in primary biliary cirrhosis.
We present the results of a retrospective review of abdominal computed tomography, ultrasound, and magnetic resonance examinations of 12 patients with primary biliary cirrhosis undertaken to determine the prevalence and clinical significance of previously reported coexistent intra-abdominal lymphadenopathy in patients with this disorder. Lymphadenopathy, in the form of bulky periportal and retroperitoneal nodes, was identified in a single patient secondary to an occult metastatic adenocarcinoma. We conclude that coexistent intra-abdominal lymphadenopathy occurring in patients with primary biliary cirrhosis is uncommon. Although it may represent a benign component of the primary disease, it may equally be due to unsuspected coexistent occult malignancy.
7789022
Can MRI predict the histopathological response in patients with osteosarcoma after the first cycle of chemotherapy?
The magnetic resonance (MR) changes after one cycle of chemotherapy were compared with the prechemotherapy studies in 39 patients with osteosarcoma, in order to identify MR changes which can be used to assess early response to chemotherapy. Measurements of total tumour volume, signal intensity, and tumour enhancement of the intra- and extraosseous tumour component were performed. Change in the amount of oedema was subjectively assessed. Changes observed were correlated with histopathological response. Changes in tumour volume and of the signal intensity of the extraosseous tumour component on T2-weighting were the only two parameters which correlated significantly (P < 0.05) with histopathological response. Increase of tumour volume is the most significant parameter and indicates poor response (sensitivity 89%, specificity 73%). Only one good responder showed increase of tumour volume. Decreased or stable tumour volume was observed in both good and poor responders. Increase of signal intensity was found exclusively in five poor responders (sensitivity 100%, specificity 23%). Decreased or stable signal intensity was observed in both good and poor responders. Changes in the amount of oedema and contrast enhancement could not predict response at an early stage. We conclude that increase of tumour volume and increase of T2 signal intensity of extraosseous tumour can be predictive for poor response. MR criteria are not helpful in the early identification of good responders.
7789023
The application of ultrasound criteria for malignancy in differentiating tuberculous cervical adenitis from metastatic nasopharyngeal carcinoma.
Tuberculous adenitis and metastatic nodes from Nasopharyngeal carcinoma may have a similar clinical presentation. Clinical examination and laboratory tests alone are unable to differentiate the two. However, ultrasound is a useful initial investigation in differentiating these two conditions. We present ultrasound appearances in 33 patients with proven tuberculous cervical adenitis and 32 patients with proven metastatic nasopharyngeal carcinoma. The ultrasound features we found useful were the distribution of the nodes, cystic change, matting and surrounding soft tissue oedema. The size, shape and internal architecture of the nodes, previously described criteria in differentiating benign from malignant nodes, did not help.
7789021
Signal changes in the intervertebral discs on MRI of the thoracolumbar spine in ankylosing spondylitis.
Contrary to standard teaching in magnetic resonance imaging (MRI), recent reports have documented calcification appearing as areas of increased signal intensity (SI) on T1-weighted images. Intervertebral disc calcification is a frequent finding on radiographs in chronic ankylosing spondylitis (AS). This study was performed to investigate the appearance of variable degrees of disc calcification in MRI. Thirty-six patients with AS of variable duration underwent an MRI scan of the thoraco-lumbar spine and the MR appearances, particularly of the discs, were compared with plain radiographs. Increased SI of the discs on T1-weighted images were found in 17 of 36 patients, occurring over a range of disc levels, and correlating with disc calcification on the radiographs in 78% of cases. This group tended to be older and have a longer duration of disease than those with normal appearing discs. Four different patterns of increased signal within the discs termed Type A (marginal), Type B (annular), Type C (central) and Type D (solid) were identified. In those with less than six discs involved Type A was the most common pattern. In those with more than six discs involved Type D was the most common pattern, suggesting a progression of disc involvement with more advanced disease. Although these findings will not affect the management of the disease, they do highlight the recently described phenomenon of calcification appearing as increased SI on T1-weighted images, likely to be related to the surface area of the calcium crystal. This should lead to the consideration of calcium in the differential diagnosis of increased SI on T1-weighted images. End-plate marrow changes were a relatively frequent finding in this study but did not correlate with the signal changes seen within the discs; in a number of cases they related to variable degrees of bony bridging.
7789020
Normal variation in the magnetic resonance imaging appearances of the sacroiliac joints: pitfalls in the diagnosis of sacroiliitis.
The purpose of this paper is to define the normal and variable appearances of the sacroiliac joints and adjacent subchondral marrow on unenhanced and enhanced Magnetic Resonance Imaging (MRI). Twenty subjects were imaged with spin-echo T1-weighted (T1), fast spin-echo T2-weighted (T2), T1-weighted with fat suppression (T1FS) and fast short tau inversion recovery (Fast STIR) sequences. Five of these subjects were imaged following intravenous Gd-DTPA administration, and the enhancement factor of the synovial compartment of the sacroiliac joint and subchondral marrow was calculated. The appearance of the cartilage of the synovial compartment on T1 and T2 images is of an intermediate signal bounded by signal void of bone cortex. On T1FS and Fast STIR images the cartilage has an intermediate to high signal. The marrow on T1, T2 and T1FS images has a homogeneous intermediate signal. T1FS images demonstrate the synovial compartment with greater clarity than T1 images. Cortical erosions and subchondral sclerosis were not demonstrated in our subjects, and partial volume artifact between the synovial and ligamentous compartments should not be interpreted as erosions. On Fast STIR images there is normally a region of high signal from the immediate subchondral marrow, which should not be interpreted as early sacroiliitis. Seven subjects demonstrated a patchy distribution of fat within the bone marrow, an appearance which alone does not indicate sacroiliitis. One subject had an accessory articular facet of the sacroiliac joint. The percentage maximal enhancement factor of the synovial compartment of the sacroiliac joint and adjacent subchondral marrow is 52% and 94% on T1FS images respectively. These figures redefine the normal maximal enhancement factors in this region of the body.
7789019
Delayed CT findings in acute renal infection.
The computed tomography (CT) findings in twelve patients with acute renal infection examined immediately and 3 h after i.v. contrast medium are reported. Three patients also had delayed scans at 6 h. Three main features were observed on the delayed scans: 1 a delayed nephrogram with streaky, wedge shaped or round high density areas. The areas of high density were at the same sites of the inhomogeneous areas of reduced density on the early scans; 2 focal contrast medium staining or a rim of increased density around abscesses; 3 focal areas of increased density at sites distant from the low density areas seen on the early scans. It is postulated that the delayed areas of increased density replace early areas of reduced density caused by ischemia due to vasospasm and/or compressing oedema of the vascular bed or by tubular obstruction. Delayed CT appears to be useful because it improves diagnostic confidence and gives a more exact evaluation of the extent of infection.
7789018
Serial changes of cystic air spaces in fibrosing alveolitis: a CT-pathological study.
In patients with cryptogenic fibrosing alveolitis (CFA), subpleural large cysts are sometimes seen within honeycombing on computed tomography (CT). These cysts may be interpreted as bullae and the coexistence of emphysema with CFA might be assumed. We evaluated whether cystic spaces in honeycombing become larger in patients with CFA on serial CT scans. CT scans were obtained in 16 patients with CFA, who had undergone two CT examinations (6 to 43 months, mean 25.1 months apart), were reviewed focusing on the changes in size of the cystic spaces in honeycombing. The mechanism of enlargement of cystic spaces was investigated using microscopic serial sections of autopsied specimens. In 15 of 16 patients, the cystic spaces in honeycombing were larger on the second examination. Histologically, stenosis of bronchioles and slit-like structures between cysts and bronchioles were detected in addition to alveolar septal dissolution and bronchiolectasis. Both the bronchiolar stenosis and the slit-like gaps have the potential to work as check-valves and increase the volume of cystic spaces. Therefore, in the evaluation of CFA, large cysts should be interpreted with caution to avoid misinterpretation of the cysts as bullae associated with emphysema. From the results of this correlative study, we suggest that a check-valve effect is an important mechanism in the formation of large cysts in honeycomb lung.
7789013
Infective endocarditis in neonates.
We studied retrospectively the predisposing factors and signs of infective endocarditis (IE) in neonates and infants younger than 3 months of age, and we suggest diagnostic criteria. The charts of 16 infants less than 3 months of age, diagnosed with IE during a 5-year period, were reviewed for possible maternal and infant risk factors and for pathognomonic clinical and laboratory features. No apparent maternal risk factors were noted. Infant risk factors were congenital heart disease (4), patent ductus arteriosus (PDA) (5), and the use of central venous catheters (14). The main clinical findings were cardiac murmurs (12), petechiae (2), skin abscesses (7), arthritis (2), hepatomegaly (9), and splenomegaly (2). Echocardiography revealed a mass or vegetation in nine patients. Of the 27 microorganisms isolated from blood, the most common were staphylococci (15) and Candida sp. (6). Urine cultures were positive in six patients and cerebrospinal fluid cultures were positive in one. Other laboratory findings were not of diagnostic value. We conclude that the main risk factors for neonatal IE are central venous catheters and congenital heart disease, including PDA. The main causative microorganisms are staphylococci and Candida sp. The main investigations of diagnostic value are blood and urine cultures and echocardiography. We propose the diagnostic categories of definite, probable, and possible cases of neonatal IE, based primarily on clinical, blood culture, and echocardiographic data.
7789012
Marked heterogeneity in Niemann-Pick disease, type C. Clinical and ultrastructural findings.
Niemann-Pick disease type C (NP-C) is an autosomal recessive lysosomal lipid storage disorder of unknown etiology. Diagnosis of NP-C is based on characteristic clinical findings and reduced fibroblast esterification of LDL-derived cholesterol. We describe three patients who demonstrate the NP-C spectrum of clinical heterogeneity in age of onset, presenting signs, pattern of organ system involvement, and natural history. In addition, electron microscopic analysis of skin biopsy specimens from these patients revealed marked variability in the extent and cellular distribution of intralysosomal storage and was suggestive of the correct diagnosis in only one case. These cases demonstrate both the limitations of electron microscopy for diagnosis of NP-C and the marked clinical variability in patients with this disorder. Practical clinical guidelines for appropriate suspicion of NP-C are presented.
7789011
Kawasaki syndrome masquerading as bacterial lymphadenitis.
We present two case reports of older children who initially presented with cervical lymphadenitis and who were eventually diagnosed and treated for Kawasaki syndrome (KS). Both children presented with unilateral cervical lymphadenopathy and fever and later developed additional clinical features of KS, including cardiac aneurysms in one of the patients. Of the five KS clinical criteria which accompany fever for 5 days, cervical lymphadenopathy of > or = 1.5 cm is the least commonly found. Both patients were treated as having bacterial adenitis prior to the diagnosis of KS. We hope to illustrate that in the case of atypical cervical lymphadenitis, KS should be carefully considered in the differential diagnosis.
7789009
Concepts of illness causality in a pediatric sample. Relationship to illness duration, frequency of hospitalization, and degree of life-threat.
In this study, we evaluated whether previous medical experience is associated with more sophisticated conceptions of illness causality among 64 children ages 4 to 16 years old. Although age and prorated IQ were found to be strongly related to children's illness causality concepts, duration of medical condition, total hospitalization days, and higher life-threat medical conditions were not associated with more sophisticated illness concepts in this pediatric sample. Using multiple regression analysis, age and IQ accounted for 59% of the variance in illness causality scores; contrary to expectations, medical experience variables (i.e., diagnosis, illness duration, hospitalizations) were not significant predictors of children's illness concepts. These findings highlight the need for pediatricians to guard against overestimating the illness concepts of children with prior medical experience.
7788996
Diagnostic value of Tc-99m (V) DMSA for chondrogenic tumors with positive Tc-99m HMDP uptake on bone scintigraphy.
Technetium-99m (V) DMSA scintigraphy was performed in 17 patients with 37 chondrogenic tumors (13 osteochondromas, 14 enchondromas, and 10 chondrosarcomas) that had previously shown uptake of Tc-99m HMDP. Technetium-99m (V) DMSA showed high uptake by all chrondrosarcomas, but low or no uptake always indicated benign chondrogenic tumors. Technetium-99m (V) DMSA scintigraphy may be superior to Tc-99m HMDP scintigraphy for distinguishing benign and malignant chondrogenic tumors, and could also be useful for diagnosing the malignant transformation of chondrogenic tumors.
7788995
I-123 MIBG imaging of metastatic carcinoid tumor from the rectum.
I-131 MIBG, a specific radiopharmaceutical agent for scintigraphic imaging and treatment of pheochromocytoma and neuroblastoma may be useful for detection of apudomas. Scintigraphy with I-123 radiolabeled MIBG was performed in a patient with metastatic carcinoid tumor from the rectum. I-123 MIBG scintigraphic findings showed multiple areas of abnormal tumor uptake of hepatic and bone metastases from the rectal carcinoid. Bone scintigraphy demonstrated multiple metastatic lesions. Computed tomography revealed multiple solid tumors of the liver. This report describes accumulation of I-123 MIBG in the liver and bone metastases from the rectal carcinoid. Radioiodine MIBG scintigraphy may be useful for detecting metastatic lesions, for evaluating postoperative recurrence, and also for the treatment of the carcinoid tumor.
7788994
Tc-99m sestamibi uptake by malignant lymphoma and slow washout.
Tc-99m sestamibi has been used to detect primary brain tumors, lung tumors, and breast cancers. The authors report a patient who had superior vena cava (SVC) syndrome and underwent Tc-99m sestamibi and Tl-201 SPECT to differentiate the tumor from thrombus in the mediastinum because of an abnormal mass lesion on a contrast enhanced CT scan. An abnormal area of increased Tc-99m sestamibi uptake in the supra azygos area was demonstrated on early and delayed SPECT imaging. The washout of tumor uptake was slow. The removed tumor was confirmed to be malignant lymphoma.
7788993
Use of Tc-99m HMPAO brain SPECT to evaluate cerebral collateral circulation during Matas test.
Five patients with traumatic carotid-cavernous fistulae and two patients with internal carotid artery aneurysms inside the cavernous sinus are presented. A quantitative method was used for the evaluation of brain collateral circulation in the anterior and middle cerebral artery territories by using Tc-99m HMPAO SPECT before and during the Matas test. It affords a more reliable quantitative measurement of reduced activity than conventional carotid angiography during the Matas test. In this study, a reduction of radioactivity of less than 15% during the Matas test did not reveal any postoperative neurological deficit after a carotid artery trapping procedure. This noninvasive method seems to be useful to determine the appropriate surgical treatment.
7788992
An approach to cerebral vasodilatory capacity in unilateral and bilateral cerebrovascular diseases using radiolabeled human serum albumin.
The acute cerebrovascular response to acetazolamide was assessed using a blood pool agent and planar dynamic imaging to evaluate cerebral vasodilatory capacity. Ten normal subjects and 12 patients with unilateral or bilateral cerebrovascular disease were studied. After the injection of radiolabeled human serum albumin, dynamic imaging of the anterior view of the head was started. Ten minutes later, 1000 mg of acetazolamide was infused. The dilatation index (the percent increase in activity at the peak response) was obtained for each cerebral hemisphere. The mean dilatation index in normal subjects was 17.1 +/- 3.2% (N = 20). The value was significantly lower in patients with multiple infarcts (7.7 +/- 1.1%, N = 8, P < 0.001), and below the normal range in two involved hemispheres of five patients with unilateral occlusive carotid artery disease and in three hemispheres of three patients with moyamoya disease. It was suggested that this simple method may be useful in assessing cerebral vasodilatory capacity in both unilateral and bilateral diseases.
7788991
Localization of infection in HIV antibody positive patients with fever. Comparison of the efficacy of Ga-67 citrate and radiolabeled human IgG.
Patients who are human immunodeficiency virus (HIV) antibody positive are at increased risk of life threatening infection. Scintigraphic imaging with Ga-67 citrate has been used to identify the presence and site of focal infection. However, focal accumulation of Ga-67 is not specific for infection. A retrospective study was performed to compare the accuracy of Ga-67 citrate and pooled human polyclonal immunoglobulin G (HIG) labeled with Tc-99m HIG and In-111 HIG in identifying infection in HIV antibody positive patients. Twenty-five studies were performed using Ga-67 and Tc-99m HIG were compared with a second group of 25 studies using In-111 HIG in HIV antibody positive patients presenting with fever, but without localizing symptoms or signs. In-111 HIG identified 20 of 22 sites of infection and also accumulated in 5 sites without infection (accuracy = 90%). This was significantly more accurate (X2, P < 0.05) than Ga-67 which identified 19 of 20 sites of infection, but accumulated in 18 sites without infection (accuracy = 74%) and Tc-99m HIG which identified infection in 11 of 20 sites, but accumulated in 8 sites without infection (accuracy = 77%). There was no significant difference between the accuracy of Ga-67 and Tc-99m HIG. From this preliminary study In-111 HIG would seem to be the best agent for identifying infection in HIV antibody positive patients with fever.
7788989
Utility of Tc-99m GSA SPECT imaging in estimation of functional volume of liver segments in health and liver diseases.
The authors examined whether there was a difference in liver function among hepatic segments in liver cirrhosis cases, and in cases of hepatocellular carcinoma (HCC) associated with liver cirrhosis. If the average counts in the lateral segment of the left lobe were set at 1, the average counts in the right upper and lower segment of the liver were 0.75 approximately 1.02 (0.89 +/- 0.09, mean +/- SD) in normal cases, 0.38 approximately 2.24 (1.01 +/- 0.39) in liver cirrhosis cases, and 0.61 approximately 2.85 (1.15 +/- 0.58) in HCC cases. There is a significant difference between normal cases and liver cirrhosis cases or HCC cases (P < 0.001). Also, in HCC cases, if the average counts in the cancer-bearing segment of the liver were set at 1, the average counts in the noncancerous segment of the liver were 0.55 approximately 2.85 (1.23 +/- 0.58), and many average counts in the cancer-bearing segment were equal to, or lower than those in the noncancerous segment. It has been found that there were significant differences in function among hepatic segments in liver cirrhosis cases, and in HCC cases. Furthermore, the liver function in the cancer-bearing segment tended to be worse due to the existence of carcinoma compared with that in the noncancerous segment.
7788988
Efficacy of hepatobiliary scintigraphy in demonstrating cholangio-colic fistulae. Is formation of internal biliary fistula related to external leak closure?
The authors present four cases of internal biliary fistulae (IBF) identified on hepatobiliary scintigraphy. All of the cases share common history of external biliary leak closure. Scintigraphy in all four cases showed a similar pattern of direct visualization of transverse colon without any significant small bowel activity. This suggests an increased frequency of IBF formation in cases with external fistulous tract closure. Retrospectively, it appears that spontaneous closure of external leak may be pathological consequence of formation of IBF involving hepatic flexure.
7788990
Tc-99m galactosyl-neoglycoalbumin hepatic scintigraphy in fulminant hepatic failure.
Tc-99m galactosyl-neoglycoalbumin (NGA) is a new liver imaging agent that specifically binds to a hepatocyte specific membrane receptor, the hepatic binding protein. Scintigraphy with Tc-99m NGA is a noninvasive method that provides functional images of the liver. This report deals with one case of fulminant hepatic failure in which hepatic scintigraphy with Tc-99m NGA predicted hepatic recovery before clinical and biochemical parameters, being a prognostic index in this patient.
7788987
Discordant findings between krypton-81m gas and Tc-99m labeled ultrafine aerosol lung ventilation SPECT in two patients with idiopathic pulmonary fibrosis.
Technegas, a newly developed ultra-fine dry dispersion of Tc-99m labeled carbon with a particle size of approximately 5 nm to 20 nm, possesses the properties for lung ventilation imaging using SPECT. The authors observed a discrepancy between krypton-81m gas and technegas lung ventilation SPECT in two patients with idiopathic pulmonary fibrosis who demonstrated heterogeneously decreased distribution of technegas without regions of high count density (focal hot spots) of tracer in their lungs in spite of the almost homogenous distribution of krypton-81m gas. This finding could be explained by the duration of radioactive gas inhalation. Technegas lung ventilation SPECT images reflected lung ventilation with tidal breathing. Conversely, Kr-81m gas lung ventilation SPECT images reflected not only lung ventilation, but also lung volumes. These two radioactive agents for lung ventilation SPECT show different findings.
7788986
Evaluation of bone metastases by Tc-99m MDP imaging in patients with stomach cancer.
The authors conducted a retrospective review of 234 bone scans of stomach cancer patients who had been diagnosed at the Seoul National University Hospital. In 106 of the 234 cases (45.3%), there were abnormal bone scan results, suggestive of bone metastases. The most common site of bone metastases was the spine, followed by the ribs, pelvis, femur, and skull. These sites were similar to those known for other malignant diseases. The incidence of bone metastases increased according to the duration of disease, especially within 12 months after diagnosis in patients with stage III gastric cancer. The incidence of bone metastases increased as the clinical stage increased. However, the incidence of metastases did not relate to gastric cancer pathologic type. The authors found 6 cases of "superscan" in the 234 bone scans (2.6%). The bone scan findings correlated positively with the level of serum alkaline phosphatase.
7788985
Eurysternum (extra-wide sternum)--a rarely recognized developmental anomaly. Scintigraphic appearances.
A rarely recognized extra-wide sternum was demonstrated by Tc-99m methylene diphosphonate bone scans in two adult patients. One patient was a 53-year-old man with prostate cancer who had no sternal symptoms or known sternal deformity. The second patient was a 41-year-old man with carcinoma of the lung whose extra-wide sternum was associated with a pectus excavatum deformity involving the lower half of the mesosternum (corpus sternum). A proper name for this developmental abnormality, "eurysternum" (eury-Greek word meaning broad; wide), is suggested. Two other patients, one with another type of wide sternum and another with a mesosternal foramen (fenestra sternii) deformity are also described. Related embryology and developmental anatomy of the sternum are reviewed.
7788983
Prominent uptake of Tl-201 by duodenal leiomyosarcoma after exercise myocardial perfusion study.
Thallium-201 SPECT performed preoperatively for the evaluation of myocardial ischemia in a 72-year-old man with duodenal leiomyosarcoma demonstrated prominent focal uptake in the abdomen. Comparing a transaxial slice of SPECT through the abdominal uptake to the CT scan, the uptake was confirmed to be corresponding to the tumor. The tumor was delineated clearly, in good contrast to the surrounding normal intestine, which showed far less Tl-201 uptake than the tumor. In the delayed SPECT performed 3 hours after injection, although the intestinal activity became perceptible, the tumor still could be differentiated from the surrounding normal intestine. In this case, the exercise might be attributable to the initial low Tl-201 uptake by the normal intestine, which might otherwise have been an obstacle to Tl-201 scintigraphy for abdominal tumor detection. This case suggests the use of exercise for avoiding unfavorable intestinal activity, and the possibility of Tl-201 SPECT for abdominal tumor imaging.
7788984
Comparison of planar, SPECT, and 3-D synthetic reprojection images. A case study.
A case study is presented in which three types of images from a Ga-67 study are compared. The Ga-67 study was performed on a patient with fever of unknown origin (FUO). Planar and SPECT images were obtained. Planar data were presented as standard 2-D images on radiographic film. The SPECT data were used to generate two sets of images: standard 2-D multiple 'slice' images presented on radiographic film and a rotating 3-D synthetic reprojection displayed on a computer monitor. Compared to the planar and SPECT images, three sites of inflammation and the path of an oblique sinus tract were best seen in the 3-D synthetic reprojection. Recognition of anatomic structures and their spatial relationships was most readily apparent when viewing the 3-D synthetic reprojection, and this method of display facilitated the rapid recognition of abnormal findings.
7788982
Characterization of chest masses by FDG positron emission tomography.
Radiographic imaging techniques have proved to be of limited value in characterizing chest masses. Likewise, scintigraphic techniques with tumor-seeking single photon emitting agents have shown marginal practical benefit. In contrast, high resolution PET with [F-18]-2-fluoro-2-D-deoxyglucose (FDG) offers a unique opportunity to distinguish benign from malignant processes by determining metabolic characteristics. PET scan results, including graphical analysis of tumor transfer constants (Patlak plot) in 21 patients with primary lung cancer, were compared to clinical outcome (histologic proof or clinical follow-up of longer than 1 year) in 54 patients who had chest masses identified by CT and/or plain film. The patients were categorized into three groups. The first group (N = 23) had primary, unknown, lung masses. Differentiation of benign from malignant tumors by PET had a sensitivity of 100% and a specificity of 67%. The second group (N = 13) had proven lung carcinoma or lymphoma and post-therapy PET scanning for recurrent tumor. In this setting, PET had a sensitivity of 83% and a specificity of 80%. The third group (N = 18) had extrathoracic malignancies and suspected pulmonary metastases. Metastatic lesions were identified with a sensitivity of 87% and specificity of 83%. Glucose uptake by normal tissue is variable and inflammatory/infectious processes can have high FDG uptake and overlap with the glucose uptake of malignant tissue. FDG PET is useful in characterizing chest tumors based on the level of their metabolic activity. Malignant tissue has a high glucose uptake. Elevated FDG uptake by an active inflammatory process may produce overlapping results.(ABSTRACT TRUNCATED AT 250 WORDS)
7788981
Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti-Yo antibody. 1. Mouse strains bearing different MHC molecules produce antibodies on immunization with recombinant Yo protein, but do not cause Purkinje cell loss.
Passive transfer of anti-Yo antibody from patients with paraneoplastic cerebellar degeneration (PCD) associated with gynecological or breast carcinoma has not been successful in inducing an animal model. We used active immunization with recombinant Yo protein of four strains of mice bearing different MHC molecules: BALB/c (H-2d), C3H (H-2k), C57BL/6 (H-2b), SJL/J (H-2s). All the strains produced high anti-Yo antibody titer but none developed cerebellar ataxia or showed Purkinje cell loss. Spleen cells from the immunized mice also reacted with recombinant protein. Because C57BL/6(nu/nu) mice produce no anti-Yo antibody, mature helper T cells are required for its production. Results suggest that antibody production in peripheral blood alone is not sufficient for the development of PCD and that MHC class II molecules function in the activation of T cells to help B cells to help B cells produce antibodies.
7788980
Intradural tumors of the cauda equina: a single institution review of clinical characteristics.
A retrospective review of 106 cases of intradural tumors of the cauda equina are presented, subdivided into 5 groups according to their histological characteristics. For each group the clinical course and long-term postoperative results were analyzed: it emerged that differential diagnosis between neurinomas, meningiomas or non-tumoral lesions is not possible based on clinical findings alone and that neuroradiological diagnosis is more accurate when MRI is employed. Long-term prognosis was always favorable with the exception of the group of ependymomas. Nevertheless, early diagnosis in the latter group of tumors gives excellent results because prognosis is apparently directly correlated to the length of preoperative clinical history.
7788979
Immune diagnosis of paraneoplastic neurological disease.
A continuous stream of new information on clinical, pathological and immunological aspects of paraneoplastic neurological syndromes has been published in recent years. In this survey, we will discuss current opinions on the value of anti-neuronal antibody detection for establishing a diagnosis of one of the paraneoplastic syndromes of the central nervous system.
7788975
Post-heatstroke parkinsonism and cerebellar dysfunction.
A case is presented of a 45-year-old woman who developed parkinsonism, cerebellar dysfunction, aphasia and flaccid paralysis secondary to heat stroke. Magnetic resonance imaging revealed irregular patchy areas of increased signal intensity in the white matter of both cerebral hemispheres and the left striatum, remaining unchanged over a follow-up period of two years. Cerebellar atrophy, while not seen on initial examination, was present on the follow-up study done one year later and became more marked after two years.
7788974
Racemose neurocysticercosis after chronic meningitis: effect of medical treatment.
A patient affected by racemous neurocysticercosis, occurring 5 years after the onset of chronic meningitis and followed by sequential MRI studies, is described. After ventriculo-peritoneal shunt, he was successfully treated with Praziquantel and Albendazole. This case may contribute to understand the natural history of the disease and stress the efficacy of medical versus surgical treatment of this lifethreatening disease.
7788973
Ossifying fibroma of the occipital bone.
A case of occipital ossifying fibroma in a 13-year-old girl is presented. Ossifying fibroma is a rare, benign, primary bone tumour that occurs most commonly in the mandible. Cranial vault location is extremely rare. To our knowledge, our patient is the second case of occipital location reported. Total surgical excision is the treatment of choice.
7788972
Complete callosal disconnection after closed head injury.
We report a patient with complete callosal disconnection syndrome after severe closed head injury. MRI showed a complete destruction of the corpus callosum throughout its length. Although traumatic callosal lesions are a frequent finding in autopsy studies, as well as in some recent MRI studies, clinical signs of callosal disconnection are rarely observed after head injuries and a complete disconnection syndrome has not been reported yet. This case study and the review of other reported cases suggest that posttraumatic callosal disconnection is probably often overlooked. Our patient had also a severe memory disorder that might be partly related to the bilateral involvement of the fornix, as this structure is closely adjacent to the posterior corpus callosum, and was also shown by MRI to be very probably damaged.
7788970
Desmoplastic low grade astrocytoma: a case report and review of literature.
A 7-year-old girl presented with focal seizures without symptoms of raised intracranial tension. Routine histological, immunocytochemical and ultrastructural methods revealed a desmoplastic low grade cerebral astrocytoma. Follow up for 2 years after biopsy did not show recruitment of neurological symptoms or signs. Biphasic tumours containing glial and mesenchymal elements have been described in the literature under various diagnostic headings. As the histologically benign variants of mixed glial and mesenchymal tumours appear to have a good prognosis, identification of these as separate entities seems imperative. With a review of literature we propose a pathological classification of mixed glial and mesenchymal tumours.
7788971
Seizures with negative phenomena.
Somatic inhibitory seizures and amnesic seizures are thought to occur rarely. We describe a patient with both types of seizures who initially presented with a clinical picture of transient ischemic attack. Neuroradiological investigations revealed a lesion probably a cavernoma located above the parietooccipital sulcus in the isthmus of cingulate gyrus. Anticonvulsant therapy eliminated both types of seizure.
7788969
Positron emission tomography in spastic diplegia.
In this study, three patients with spastic diplegia were examined with magnetic resonance imaging (MRI) and positron emission tomography (PET), using the steady state technique with 15O. Two of them had untractable seizures and mental retardation. On MRI the cortical structures were normal; increased T2 signals in the periventricular white matter in the second patient were the main findings. PET scan showed in the two patients with a seizure disorder and mental retardation a large left cortical area of decreased regional blood flow and oxygen consumption during the interictal phase. The third patient without epileptic spells had a normal PET scan examination. It is concluded that the epileptic disorder in two of our cases is due to an additional cortical lesion, while the spastic diplegia is caused by subcortical white matter destruction.
7788968
An unusual case of central nervous system cryptococcosis.
Opportunistic infections of the central nervous system (CNS) in immunocompromised patients often represent a diagnostic and therapeutic challenge due to the variety of possible infectious agents causing CNS disease. We report the case of a severely immunocompromised 43-year-old woman presenting with headache, confusion, abnormal CSF findings (cell count 237/mm3 with 50% eosinophils and elevated protein), multiple contrast enhancing lesions on CT and MRI in the basal ganglia, and serologic findings compatible with latent or reactivated toxoplasmosis with high IgA and IgG antibody titers against Toxoplasma gondii in whom a final diagnosis of CNS cryptococcosis was made. This case illustrates the considerable difficulties in the differential diagnosis of opportunistic CNS infection in the immunocompromised host. We conclude from our report that (1) the diagnosis of toxoplasma encephalitis should not be based on serological findings but rather be proven by either PCR, mouse inoculation or brain biopsy, (2) CNS cryptococcosis can be associated with marked CSF eosinophilia and multiple cryptococcomas, and (3) cryptococcomas can persist on CT and MRI despite successful antifungal treatment.
7788967
'Lewy body disease': clinico-pathological correlations in 18 consecutive cases of Parkinson's disease with and without dementia.
One of the characteristic histological features of Parkinson's disease (PD), with or without dementia, is the presence of Lewy bodies (LBs) in the brainstem and neocortical and limbic structures. They are often accompanied by Alzheimer type pathology (ATP). In the present retrospective study the clinical features and post-mortem findings of 18 consecutive and unselected PD patients were compared, with special reference to the frequent but not exclusive association of LBs with ATP in Lewy body disease (LBD). LBD is the term applied to a particular pattern of neuronal degeneration associated with LBs. In this study of idiopathic PD patients ATP seems to be the major determinant of the cognitive decline in most patients. Cortical Lewy Bodies (CLBs) were present in all patients reviewed, whether or not dementia was present. It was not possible to distinguish a specific pattern in the cognitive or psychopathological symptoms of dementia that would differentiate LBD from Alzheimer's disease (AD). Although in most cases hippocampal CA2-3 ubiquitin immunoreactive neurites were observed, here again there was no correlation with the presence of dementia.
7788964
Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti-Yo antibody. 2. Passive transfer of murine mononuclear cells activated with recombinant Yo protein to paraneoplastic cerebellar degeneration lymphocytes in severe combined immunodeficiency mice.
Passive transfer of serum IgG or mononuclear cells from peripheral blood of a patient with paraneoplastic cerebellar degeneration (PCD) to rodents was carried out in order to examine the role of anti-Purkinje cell antibody (anti-Yo antibody) present in serum and cerebrospinal fluid of PCD patients. After a single injection of IgG into mouse brain, it was taken up by Purkinje cells and remained there for more than 36 h without Purkinje cell loss. Injection of PCD IgG together with complement or lipopolysaccharide-activated human macrophages or rat mononuclear cells into rat ventricles did not cause Purkinje cell loss. We also studied passive transfer of the PCD patient's lymphocytes to mice with severe combined immunodeficiency (SCID). We constructed a recombinant Yo fusion protein that has the leucine-zipper protein (Yo protein), the common epitope for anti-Yo antibody for immunizing mice, and that resulted in production of significant amounts of anti-Yo antibody. Spleen cells from these Yo protein immunized mice were injected intravenously or intracerebrally into naive mice that subsequently showed no neurological symptoms or loss of Purkinje cells. We conclude that the anti-Yo antibody, either in combination with or without complement or activated mononuclear cells, cannot be the sole cause of Purkinje cell loss.
7788965
Anti-tumour therapy in paraneoplastic neurological disease.
Paraneoplastic neurological syndromes have attracted attention in recent years. Detection of auto-antibodies directed against CNS and PNS structures have suggested an autoimmune etiology. This review is based on reports from the past 10 years and summarizes the therapeutic results in 258 patients suffering from paraneoplastic neurological disease including paraneoplastic encephalomyelitis, sensory neuronopathy, cerebellar degeneration, motor neurone disease and stiff man syndrome. The results show that in some entities such as Lambert-Eaton syndrome successful treatment can be expected. In other syndromes such as subacute sensory neuronopathy or paraneoplastic cerebellar degeneration therapeutic success varies from 5 to 10%.
7788962
Higher in-hospital mortality in female patients following coronary artery bypass surgery: a population-based study. Provincial Adult Cardiac Care Network of Ontario.
This study examined the relationship between gender and in-hospital mortality using data from patients undergoing coronary artery bypass surgery (CABS) in the province of Ontario. All patients who underwent CABS between April 1, 1991 and March 31, 1992 at the 9 cardiac surgery institutions were included for study (n = 5,175). The unadjusted in-hospital mortality rate was 3.3% and was higher among females (5.3%) than males (2.8%). Using logistic regression analysis to adjust for several predictors of in-hospital mortality the odds ratio estimate (OR) for female sex was 1.55 and was statistically significant (95% confidence interval (CI) 1.09 to 2.20). Women experienced rates of in-hospital mortality that are 1.6 times greater than males following bypass surgery after case-mix adjustment for age, anatomical disease severity, anginal class, and comorbid conditions. Severe unstable angina had the greatest potential contribution to in-hospital mortality (OR = 7.51, 95% CI = 3.71-15.23) and was more prevalent in women, indicating that excess mortality may be due to delayed diagnosis in women.
7788963
An early-onset recessive cerebellar disorder with distal amyotrophy and, in two patients, gross myoclonia: a probable ataxia telangiectasia variant.
We report a family of 4 siblings from a non-consanguineous marriage, presenting with an early onset recessive cerebellar ataxia and progressive distal limb wasting. Ocular or other telangiectasias were absent. There were neither frequent infections nor immunodeficiencies. The two youngest patients exhibited an incapacitating myoclonus which abated markedly after 20 years. Late onset diabetes was demonstrated in 3 patients. Hypogonadism was not a feature and there was a prolonged survival in the 4 patients. The oldest sibling died of a pancreatic adenocarcinoma. alpha-Fetoprotein was elevated with normal carcinoembryonic antigen values in three patients. Cytogenetic analysis and radioresistant DNA synthesis was compatible with the diagnosis of ataxia-telagiectasia. This family probably represents a rare variant of ataxia-telangiectasia.
7788961
The effect of interleukin-2 on suppressor T lymphocytes in autoimmune thyroid disease.
We have investigated the effects of interleukin-2 (IL-2) on the activation of suppressor T lymphocytes in autoimmune thyroid disease (AITD), with insulin-dependent diabetes mellitus (IDDM) as an autoimmune disease control; this was accomplished by measuring the expression of major histocompatibility complex class II (HLA-DR), CD25 (IL-2 alpha receptor (R)), and IL-2 beta R expression on their surfaces by flow cytometric analysis. Peripheral blood mononuclear cells (PBMC), obtained from 10 patients with Graves' disease (GD), 11 with Hashimoto's thyroiditis (HT), 9 with insulin-dependent diabetes mellitus (IDDM), and 10 normal persons (N), were cultured for 7 d in the presence or absence of IL-2 at a final concentration of 50 U/mL. CD8+ cells were isolated from cultured PBMC with immunomagnetic beads, and were stained with fluorescent-conjugated monoclonal antibodies (anti-CD11b, anti-IL-2 alpha R, anti-IL-2 beta R, and anti-HLA-DR); the activation of CD8+CD11b+ ("suppressor") T cells (Ts) by IL-2 was then analyzed on a flow cytometer. In the absence of IL-2, i.e., in the autologous mixed lymphocyte reaction (AMLR), Ts from patients with GD, HT, and IDDM showed significantly lower activation as compared to N when analyzed by HLA-DR expression, but were not significantly different when IL-2R expression was measured. We determined the Stimulation Index (SI) of the activation of T lymphocytes by IL-2 for comparison between N and patients. With stimulation of 50 U/mL of IL-2, SI of HLA-DR+ Ts was significantly (p < 0.05 to 0.01) lower in GD, HT, and IDDM as compared with N.(ABSTRACT TRUNCATED AT 250 WORDS)
7788959
Does injectable gold retard radiologic evidence of joint damage in psoriatic arthritis?
The aim of this investigation has been to assess whether gold therapy prevents radiologic progression of psoriatic arthritis (PsA) over a period of 2 y. Eighteen patients (11 males, 7 females, mean age 42 y, DD 6.5 y) who were initiated on intramuscular gold during their attendance at the Psoriatic Arthritis Clinic were studied. For each gold-treated patient, 2 matched control patients, who had never had gold therapy, were identified from the PsA database. The control patients were similar to the patient population in gender, age, disease duration, number of actively inflamed joints, radiologic score and other medications used, and were followed in the clinic for at least 24 months. Actively-inflamed joint count decreased by > or = 40% in 9 of 18 gold-treated patients at 12 months. Seven patients continued gold for 24 months, while 11 discontinued gold for either lack of efficacy (4) or side effects (7). A comparison of the change in radiographic evidence of damage in the peripheral joints between the 18 gold-treated patients and the 36 controls revealed that there was no statistical difference in disease progression. These results suggest that gold therapy does not prevent the progression of damage in patients with psoriatic arthritis.
7788960
Production of acyl-carnitines from the metabolism of [U-14C]3-methyl-2-oxopentanoate by rat liver and skeletal muscle mitochondria.
A sensitive method of continuous on-line radio-high performance liquid chromatography (HPLC) was used to detect the specific radio-labelled acyl-carnitine esters derived from the oxidation of [U-14C]3-methyl-2-oxopentanoate by rat liver and muscle mitochondrial fractions. The recoveries of carnitine, acetyl-carnitine, propionyl-carnitine, 2-methylbutyryl-carnitine, and hexanoyl-carnitine were 98.7% (+/- 5.4; SEM, n = 3), 91.4% (+/- 7.6), 89.4% (+/- 5.2), 84.6% (+/- 6.8), and 87.9% (+/- 7.8), respectively, from quenched mitochondrial incubations. This method demonstrated that rat liver and muscle mitochondria generate acetyl-carnitine, propionyl-carnitine and 2-methylbutyryl-carnitine when incubated with [U-14C]3-methyl-2-oxopentanoate in the presence of carnitine. The production of acetyl-carnitine was almost similar in the 2 tissues. Muscle mitochondria produced higher amounts of propionyl-carnitine and 2-methylbutyryl-carnitine than liver mitochondria. These observations suggest a limited utilization of propionyl-CoA by muscle mitochondria which, through a mechanism of feed-back inhibition, may have contributed to the accumulation of 2-methylbutyryl-CoA. This study provides further evidence for the importance of carnitine in the modulation of the mitochondrial [acyl-CoA/[CoA] pool.
7788958
Clarithromycin versus cefaclor in lower respiratory tract infections. The Canadian Bronchitis Study Group.
A randomized study was done to compare the efficacy of clarithromycin 250 mg or 500 mg b.i.d., vs. cefaclor 250 mg or 500 mg t.i.d. for 7-14 d in 197 evaluable patients with lower respiratory tract infection. Ninety-five patients received clarithromycin, 88 with acute bronchitis or exacerbation of chronic bronchitis, and 7 with pneumonia. One hundred and two patients received cefaclor, 86 with bronchitis and 16 with pneumonia. Ten patients (10.5%) in the clarithromycin group did not complete the trial, 5 (5.3%) because of adverse event, and 3 (3.2%) because of clinical failure. Similarly, 11 patients (10.8%) did not complete cefaclor, 2 (2%) because of adverse event, and 7 (6.9%) because of clinical failure. Clinical cure or improvement was observed in 90 (94.7%) of patients on clarithromycin vs. 92 (90.2%) on cefaclor, p = 0.66. Bacteriologic cure was seen in 26/36 patients (72.2%) on clarithromycin vs. 28/40 patients (70%) on cefaclor, p = 0.28. Clarithromycin is just as effective as cefaclor for lower respiratory tract infections and is well tolerated.
7788957
Allogeneic bone marrow transplantation for severe aplastic anemia: the Vancouver experience.
We report a retrospective analysis of the experience of a single centre in treating severe aplastic anemia (SAA) with allogeneic bone marrow transplant (BMT). Between 1982 and 1992, we transplanted 21 patients with SAA (14 males, 7 females); median age at BMT was 15 y (range 2-40 y); median time from diagnosis of SAA to BMT was 29 d (range 6 d-5.5 y). Thirteen patients had received multiple transfusions before BMT. Patients were conditioned with cyclophosphamide 50 mg/kg for 4 d, +/- total body irradiation 300-500 cGy as a single fraction; 1 patient received total nodal irradiation (750 cGy) plus antithymocyte globulin. Sixteen patients received bone marrow from human leucocyte antigen (HLA)-identical siblings, 3 from haplo-identical parents, and 2 from unrelated volunteer donors; graft-versus-host disease (GVHD) prophylaxis was variable. Three patients failed to fully engraft following BMT; 2 achieved successful engraftment following a second BMT. Six of 20 evaluable patients (30%) developed grade II-IV acute GVHD, of whom 3 died; 3 patients developed limited and 5 patients (31%) developed extensive chronic GVHD, of whom 1 died. Fourteen patients (67%) are alive and well following BMT with a median follow-up of 6 y (range 2.1-11 y). Survival was superior in patients receiving sibling-donor BMT (75%) compared with those receiving parent- or unrelated-donor BMT (40%). We conclude that allogeneic BMT remains an important mode of treatment for SAA, but long-term survival remains limited by graft failure and GVHD.
7788956
Inhaled nitric oxide monitoring.
Recently, inhaled nitric oxide (NO) became clinically available for the treatment of persistent pulmonary hypertension of the newborn. Such use requires administration and continuous monitoring of a very low concentration of NO to prevent potential toxicity. Since limited data on the reliability of NO monitoring devices are available, we evaluated the performance of a chemiluminescent and electrochemical sensor NO analyzer in a patient ventilator circuit. The chemiluminescence analyzer readings were significantly altered by the oxygen concentration in the ventilator circuit. When the FiO2 was increased from 0.21 to 1, a 4.5% +/- 0.3 decrease in the NO readings was found (p < 0.01). Similarly, adding humidity to the circuit, reduced the NO readings by 4.8% +/- 0.9 (p < 0.01). The effect of gas pressure was proportional to its magnitude but independent of whether a pulsatile or continuous gas flow was provided. At a mean airway pressure of 15 cm H2O, the NO readings increased by 3.94% +/- 0.05 (NO = 10 parts per million) and 3.97% +/- 0.02 (40 parts per million) (p < 0.01). The electrochemical sensor NO readings were directly proportional to the ventilator circuit pressure but independent of whether a pulsatile or continuous gas flow was provided. At a mean airway pressure of 15 cm H2O, the NO reading was increased by 25.39% +/- 0.04 (NO = 40 parts per million) (p < 0.01) and 1.07% +/- 0.16 (NO = 10 parts per million) (p NS). The greatest difference with NO = 10 parts per million from baseline was found at a mean airway pressure of 6 cm H2O (6.67% +/- 0.23; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
7788955
Evaluation of acute haemodynamic response to high-dose naloxone in young hypertensive and normotensive humans.
Cardiac output is increased in many young subjects with mild essential hypertension. The purpose of these experiments was to determine if activation of endogenous endorphin systems contributes to this increase. We investigated the acute effects of the opioid antagonist, naloxone, on Doppler-derived stroke volume, cardiac output and systemic blood pressure in young hypertensive (n = 9) and normotensive (n = 9) subjects. On two separate sessions, naloxone (0.4 mg/kg) was administered intravenously over 10 min to resting subjects according to a random, double-blind study design. Stroke volume and cardiac output were determined before and 10 min after the injection; heart rate and blood pressure were measured at 1 min intervals before and up to 20 min after the injection. Baseline blood pressure, stroke volume, and cardiac output were higher in hypertensive than in normotensive subjects. Naloxone had no immediate effect on blood pressure, heart rate, stroke volume, or total peripheral resistance in either group. These results indicate that: (1) naloxone has no immediate haemodynamic effect in young hypertensive or normotensive subjects, and (2) the higher stroke volume and cardiac output of young subjects with mild essential hypertension cannot be attributed to activation of endogenous opioid systems that are antagonized by naloxone.
7788953
A case of cardiac sarcoidosis with remarkable atrophy of the left ventricular septum on two-dimensional echocardiography.
Sarcoidosis is a multisystem granulomatous disorder of unknown etiology which mainly affects the lungs, skin, the lymphoreticular system, and the heart. We report a case of cardiac sarcoidosis in which a remarkably thin ventricular septum was demonstrated on two-dimensional echocardiography.
7788952
Pulmonary venous flow in constrictive pericarditis.
A 35-year-old white female patient presented with radiation-induced constrictive pericarditis. Intraoperative transesophageal echocardiography revealed a uniphasic diastolic flow pattern. This pulmonary flow pattern reverted to a normal biphasic systolic/diastolic profile immediately following radical pericardiectomy. This abnormal flow pattern was previously described as typical for restrictive cardiomyopathy. However, in this case it is most likely due to a marked decrease in left atrial compliance induced by the thick fibrous scar encasing the atrial.
7788951
Pathology of tricuspid valve stenosis and pure tricuspid regurgitation--Part III.
This three-part article examines the histologic and morphologic basis for stenotic and purely regurgitant tricuspid valves. In Part III, morphometric analysis of tricuspid valve annular circumference, leaflet area, and the product of annular circumference and leaflet area are shown to be useful in establishing etiology for the purely regurgitant tricuspid valves and in assessing the anatomic basis of pure tricuspid regurgitation in the presence of mitral stenosis.
7788950
Effect of precordial electrocardiographic electrode placement on ST-segment measurement during exercise.
Research protocols often utilize serial exercise testing to examine the efficacy of anti-ischemic therapies. These tests, however, are prone to multiple sources of bias. This investigation sought to determine the influence of varying precordial electrocardiographic (ECG) electrode placement on the detection of exercise-induced ST-segment shifts. Fifteen coronary artery disease patients with abnormal exercise tests were studied. Based on the previous exercise test, the precordial electrode position exhibiting the greatest ST-segment shift was selected as the reference electrode. Four additional electrodes were placed around this reference electrode and exercise testing was performed. ECG strips were recorded every minute. The time-to-onset and -offset of ischemic-type ST-segment depression was recorded. ST-segment depression was recorded during exercise from the reference electrode in 12 of 15 patients. Ischemic-type ST-depression was also recorded in each of these 12 patients with the surrounding electrodes; however, the time-to-onset detected by all four surrounding electrodes concurred in only 5 of 12 (42%) patients. The time-to-offset of the ST-segment depression concurred in 9 of 12 (75%) patients. Serial ECGs recorded from similar but not exactly the same precordial ECG electrode position should yield similar results for the detection of ischemia, but time-to-onset or -offset of ischemia may differ by 60 s or more. Small changes in the time-to-onset and -offset of ischemia should not be considered reliable indicators of anti-ischemia efficacy.
7788949
Transesophageal echocardiographically guided atrial transseptal catheterization in patients with normal-sized atria: incidence of complications.
The incidence of cardiac complications from atrial transseptal catheterization has never been quantified in patients with normal-sized atria. Series defining the complication rate are derived from diseased hearts with structural changes that may alter the complication rate of the procedure. The generation of a standardized incidence of perforation in a population of structurally normal atria has important implications. A total of 46 atrial transseptal catheterizations guided by transesophageal echocardiography (TEE) for radiofrequency ablation of left-sided accessory pathways was performed in 42 patients during a 3-year period (1990-1993). Clinical and echocardiographic data were analyzed, with special attention given to TEE reports pre- and post-transseptal catheterization. Only one complication occurred in the 46 procedures (2.2%): a perforation of the left atrium that led to pericardial effusion and cardiac tamponade. In a small series of patients with normal sized atria, we have demonstrated that TEE-guided transseptal catheterization in a procedure with a low complication rate.
7788948
Effects of treatment with lovastatin and pravastatin on daytime cognitive performance.
The HMG-CoA reductase inhibitors lovastatin and pravastatin have both proven to be effective and well tolerated in the treatment of hypercholesterolemia. To evaluate whether lovastatin or pravastatin might affect daytime cognitive function, a double-blind, placebo-controlled, two-period, incomplete block, crossover study was performed in 36 patients (24 per treatment) with primary hypercholesterolemia. Patients received placebo, lovastatin (40 mg), or pravastatin (40 mg) for 4 weeks. Following a 1-week washout period, patients were crossed over to either lovastatin, pravastatin, or placebo for an additional 4 weeks. Mental performance tests (digit symbol substitution, choice reaction time, auditory vigilance, selective reminding word recall, finger tapping), visual analogue rating scales, and the Profile of Mood States were administered before test drug administration and after 2 and 4 weeks of each treatment. After 4 weeks, no statistically significant differences between treatments in changes from baseline were observed on any parameter with the exception of digit symbol substitution, for which lovastatin and pravastatin were both significantly better than placebo but did not differ from each other. Low-density lipoprotein cholesterol was reduced 38% by lovastatin and 30% by pravastatin. In summary, neither of these chemically distinct HMG-CoA reductase inhibitors impaired daytime cognitive performance after 4 weeks of treatment in patients with primary hypercholesterolemia.
7788947
The influence of angiographically demonstrated coronary collaterals on the results of stress echocardiography.
Previous studies using thallium-201 scintigraphy have suggested that angiographic coronary collaterals can protect against the development of stress-induced perfusion abnormalities, but the effect of collaterals on stress echocardiography (SECHO) has not been determined. In this study, 21 consecutive patients referred for cardiac catheterization underwent SECHO and coronary angiography. Of the 21 study patients, there was a total of 16 significantly obstructed coronary arteries (> or = 70% stenosis) in 14 patients. SECHO revealed stress-induced wall motion abnormalities in the distribution of seven of nine obstructed coronary vessels without angiographic collaterals, but in only one of seven vessels with collaterals (p < 0.05). Six of eight obstructed vessels not associated with a stress-induced wall motion abnormality had collaterals, whereas only one of eight obstructed vessels associated with a stress-induced wall motion abnormality had collaterals. We conclude that (1) angiographically demonstrated coronary collaterals can protect against the development of stress-induced wall motion abnormalities despite the presence of a high-grade coronary artery obstruction, and (2) the lack of a stress-induced wall motion abnormality on SECHO in the perfusion territory of an obstructed vessel may suggest the presence of adequate collateral perfusion.
7788946
Prognostic significance of right ventricular dysfunction in patients with acute inferior myocardial infarction and right ventricular involvement.
Little is known about the influence of right ventricular (RV) dysfunction on prognosis of patients with acute inferior myocardial infarction (IMI) and RV involvement. Therefore, 99 consecutive patients (mean age 56.6 +/- 3.4 years) with RV involvement during acute IMI were followed for a 12-month period to clarify the influence of acute RV dysfunction on short- and long-term survivals. Forty-one patients with IMI evolved with severe arterial hypotension due to RV dysfunction, while 58 patients had no hemodynamic impairment due to RV involvement. Basal hemodynamic data (mean +/- SD) for patients with RV dysfunction were blood pressure (BP) 92/59 +/- 22/20 mmHg, systemic vascular resistance (SVR) 2314 +/- 252 dynes.s.cm-5, and cardiac index (CI) 1.3 +/- 0.3 l/min/m2. Patients without RV dysfunction demonstrated BP 113/74 +/- 20/16 mmHg (p < or = 0.05), SVR 1324 +/- 354 dynes.s.cm-5 (p < or = 0.01), and CI 2.6 +/- 0.5 l/min/m2 (p < or = 0.05). Angiographic differences noted were that hemodynamically compromised patients showed lower RV ejection fractions (0.27 +/- 0.08) than patients without hemodynamic disturbance [0.41 +/- 0.11 (p < or = 0.05)]; however, left ventricular ejection fractions were 0.48 +/- 0.10 and 0.52 +/- 0.12, respectively. Short- and long-term mortality rates were assessed during the follow-up period. Patients with hemodynamic impairment due to RV infarction had a higher mortality rate for the first month and for 11 subsequent months post MI than patients without hemodynamic impairment, that is 24.4 vs. 6.9 and 14.6 (p <or = 0.05) vs. 3.4 (p < or = 0.05), respect ively.(ABSTRACT TRUNCATED AT 250 WORDS)
7788945
Sudden cardiac death in patients with hypertrophic cardiomyopathy: from bench to bedside with an emphasis on genetic markers.
Hypertrophic cardiomyopathy (HCM) is the most common cause of death in the young, particularly in young competitive athletes. Death often occurs suddenly in asymptomatic, apparently healthy individuals. Several clinical parameters as well as genetic factors have been characterized that can identify those HCM patients who are at high risk for sudden cardiac death (SCD). The clinical parameters that have some predictive values for SCD in HCM patients are the following: a prior history of SCD, a family history of SCD, history of syncope, symptomatic ventricular tachycardia on Holter monitoring, inducible ventricular tachycardia during electrophysiologic studies, and myocardial ischemia in children with HCM. Recent identification of mutations in the beta myosin heavy chain gene and genotype-phenotype correlation in HCM patients have shown that the beta myosin heavy chain mutations are also prognosticators in HCM families. Several mutations such as Arg403Gln and Arg719Gln are associated with a high incidence of SCD, while Leu908Val mutation is associated with a benign course and a low incidence of SCD in HCM families. Additional genetic factors such as a polymorphism in angiotensin-converting enzyme I gene may also contribute to a high incidence of SCD in HCM families. Identification and characterization of HCM patients at high risk for SCD provide the opportunity to render prophylactic therapeutic interventions, such as implantation of defibrillators, in these individuals.
7788944
Unstable angina: cost of conservative and invasive strategies using TIMI3 B as a model.
Obviously, conservative therapy would be less expensive than invasive therapy if patients were held in the conservative category and received only medical therapy along with exercise test with thallium. However, based on the TIMI 3 B outcomes, costs are similar (but not equal) even if one attempts a conservative strategy since a significant number of patients in the early conservative arm underwent angiography (64 patients) and PTCA (26 patients) or surgery (24 patients) and the number of days for rehospitalization was greater in the early conservative than in the early invasive group. I believe the TIMI 3 B study reflects the reality of clinical practice in 1995. It seems to me that either strategy is acceptable both from the medical and economic outcome standpoints. Given the model used here, I do not think that the early invasive strategy will ever be cheaper than the early conservative strategy unless all of the patients in the early conservative strategy who eventually are revascularized have CABG, and all of the patients in the early invasive strategy who are revascularized have PTCA.
7788943
Mastoidectomy audit: results of the Royal College of surgeons of England comparative audit of ENT surgery.
This paper presents the results of a national comparative audit of mastoid surgery, retrospectively analysing 611 operations by 55 consultants. Confidentiality for both patient and surgeon was assured. For cholesteatoma 80% of mastoidectomies performed were open cavity procedures and for other middle ear disease 58% used an intact canal wall technique. Thirty-two surgeons used only an open cavity mastoidectomy for cholesteatoma during the period of the audit. There was a statistically significantly greater number of wet ears with open cavities than with closed cavities, but the frequency of the operator did not correlate with the dry ear rate. Ten serious complications (facial palsy and dead ear) were recorded. All occurred in open cavity mastoidectomies. The post-operative hearing status was unknown in 40% of patients.
7788942
General primer-mediated polymerase chain reaction for simultaneous detection and typing of human papillomavirus DNA in laryngeal squamous cell carcinomas.
The aim of this study was to investigate the prevalence of different human papillomavirus (HPV) types in laryngeal squamous cell carcinomas using general primer-mediated polymerase chain reaction (PCR). Tumour sections from 42 patients with laryngeal carcinomas were investigated. For HPV DNA amplification, consensus primers were used which were directed to the L1 coding region of the HPV genome. Analysis of the PCR products was done using 2% agarose gel electrophoresis followed by restriction enzyme analysis to identify different HPV types. Amplification of the human TGF-beta 1 DNA was successfully performed in 36/42 (85.7%) of samples confirming the presence of sufficient DNA for viral amplification. HPV DNA was detected in 8/36 (22.2%) of the tumours examined (three HPV-6, two HPV-16, one HPV-11, two unknown HPV types). HPV DNA was not detected in any of the non-neoplastic laryngeal mucosa which was used as control (n = 15). Fifty per cent of women had HPV-positive tumours compared with 8% of men (chi2 = 5.8, P < 0.05). Our data indicate that while the overall prevalence of HPV in laryngeal carcinomas is fairly high (22.2%), the frequency of high-risk types (HPV-16 & HPV-18) is low (5.5%). HPV probably acts as a promoter in the multistep process of carcinogenesis in squamous mucosal cells of the larynx.
7788941
Referral patterns in vestibular schwannomas.
The investigation and treatment of vestibular schwannomas is an increasingly specialized area in which major advances have been seen over recent years. The effect of these advances on the referral patterns to a centre specializing in such surgery is reviewed. The proportion of referrals with a known diagnosis has increased substantially, allowing the specialist centre to focus on appropriate management rather than diagnosis. The vast majority of vestibular schwannomas are referred by otolaryngologists. The caseload referred by neurologists or neurosurgeons have different presenting symptoms. The incidence of vestibular schwannoma in the Cambridge district is found to be 1 per 50,000 population per year. This is a higher incidence than that recorded in other studies. This may be due to a tight diagnostic strategy and the high level of clinical awareness of the local general practitioners.
7788940
Piriform aperture surgery for alar collapse.
The region of maximum resistance in the respiratory tract is in the anterior part of the nose, and this area has been termed the nasal valve. Inspiratory narrowing of this area, known as alar or nasal valve collapse can produce the symptom of obstruction, and may be very difficult to correct. The anatomy and physiology of the nasal valve are discussed followed by the author's technique for correction of a common problem leading to alar collapse; a narrow piriform aperture, which is often associated with a prominent web at the muco-cutaneous junction.
7788938
Is otoscopy reliable? A structured teaching method to improve otoscopic accuracy in trainees.
Otoscopy is an important skill for primary care physicians and otologists. Until now, training has been by repeated exposure to patients with ear disease. Structured instruction in how to assess an ear has not previously been reported. Not-diseased ears and those with varying types of chronic (suppurative) otitis media were chosen to be photographed as this is an important condition to be able to diagnose and in which pneumatic otoscopy has no role. Two sets of 30 slides of equal difficulty were shown to 10 trainees, one before and one after structured teaching. The overall error rate fell from 44 to 21% (P < 0.001). Most importantly, the error rate in assessing ear activity fell from 35 to 17% (P < 0.05). In conclusion, a structured approach to otoscopy has been shown to improve the diagnostic ability of trainess tested with photographs of ears with chronic otitis media. Such a teaching approach is likely to be equally beneficial to other otological conditions and to live otoscopy.
7788939
The Glasgow benefit plot used to assess the effect of bilateral stapedectomy.
The Glasgow benefit plot has encouraged surgeons to look at the results of their surgery from a more functional standpoint rather than in purely technical terms. Our aim was to use the plot to examine the efficacy of second side stapedectomy. A retrospective study of 17 second side stapedectomies showed that the addition of the second operation significantly increased the chances of achieving at least one 'normal' hearing ear and made 'normal' and symmetrical hearing possible.
7788937
Speech discrimination in patients with Bell's palsy and a paralysed stapedius muscle.
The contraction of the stapedius muscle results in a frequency dependant attenuation of sound through the middle ear. Idiopathic facial nerve paralysis (Bell's palsy) usually results in a paralysis of the stapedius muscle. This prospective study included 119 patients presenting with Bell's palsy over an 18-month period. After applying exclusion criteria, 80 patients with normal pure-tone audiograms underwent speech audiometry. This was performed on presentation and after recovery of the facial nerve palsy. Fifty-six patients (70%) with an absent stapedius reflex showed marked 'roll-over' from means of 98-49% on their speech audiogram. This resolved completely with recovery of the facial nerve palsy and return of the stapedial reflex. To determine whether this effect was due primarily to the paralysis of the stapedius muscle or to an associated polyneuropathy, a second study on six normal patients was done. These patients had both ears (12 in total) tested with speech filtered to simulate a paralysed stapedius muscle. This resulted in a mean 'roll-over' from 90.9 to 59.9%. The magnitude of this roll-over (31%) was only two-thirds of that seen in Bell's palsy patients (49%) with the difference between these means statistically significant (P < 0.05). This suggests that Bell's palsy, usually considered a mononeuropathy, involves certain of the auditory fibres of the eighth nerve and is a polyneuropathy. Stapedius function is important in speech discrimination at higher levels of sound intensity such as speech in noise and severing the stapedius tendon in stapes surgery may affect speech discrimination after successful surgery.
7788936
Chondrosarcoma of the temporal bone.
Eight patients with a chondrosarcoma of the temporal bone have been treated at the National Hospital for Neurology and Neurosurgery over a 16-year-period. Patients usually presented with symptoms and signs of lower cranial nerve palsies, though in most cases these resolved after surgery. This result, combined with the fact long-term survival can be achieved, makes surgical treatment of these tumours the best option, as the response to primary radiotherapy is uncertain. Surgical access is difficult, but an infratemporal approach is probably the most satisfactory. The use of post-operative adjuvant radiotherapy may provide some benefit. Long-term follow-up is necessary, and for this magnetic resonance imaging (MRI) is preferable to computed tomography (CT) scanning.
7788935
Genetics of familial and non-familial skull base tumours.
Many tumours of the skull base, including schwannomas, paragangliomas, meningiomas and anterior pituitary tumours occur both as sporadic tumours and in clear cut familial syndromes. These cancers' highly penetrant dominantly inherited syndromes have proven to be a rich resource for locating tumour genes, most of which are of the tumour suppressor type. Recently, the gene for type 2 neurofibromatosis (NF2) was isolated by the technique of positional cloning. The NF2 gene has now been demonstrated to be involved in the pathogenesis of both familial and non-familial vestibular schwannomas as well as meningiomas. The presence of inactivating mutations within this gene suggests that it acts as a tumour suppressor and the mechanism has been shown to comply with a 'two hit' mutation model. Hereditary tumours constitute a small proportion of all cases, but evidence from studies of tumours such as vestibular schwannoma and meningioma have shown that their genes are also relevant to the much more common non-familial forms of the same tumour. This paper briefly describes the approach to locating tumour genes, and reviews our current knowledge regarding the chromosomal location and function of genes responsible for familial tumours involving the skull base. The genetic mechanisms of tumourigenesis are discussed as are the prospects for the development of novel forms of diagnosis and treatment.
7788934
Over-expression of tumour suppressor gene p53 in laryngeal squamous cell carcinomas and its prognostic significance.
p53 is a nuclear phosphoprotein which acts as a tumour suppressor factor, regulating cell growth and division. Mutations in the p53 gene appear to be the most common genetic alterations in human cancer. The aim of this study was to investigate p53 expression in laryngeal squamous cell carcinomas and to assess its role as a marker of prognostic significance. Using immunohistochemical staining techniques, a series of laryngeal carcinomas (n = 87) were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. p53 over-expression was noted in 50 biopsies of laryngeal carcinomas (57.5%) but not in any of the non-neoplastic laryngeal mucosa which were used as the control. There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of the cancers including: site of tumour, TNM staging, differentiation grading and tumour recurrence. These findings indicate that p53 expression is strongly associated with carcinoma cells and not with normal cells in the larynx. However, p53 expression is probably unrelated to the biological aggressiveness of these tumours.
7788933
Short- and long-term outcomes of uvulopalatopharyngoplasty for snoring.
Uvulopalatopharyngoplasty is a well established and highly successful operation in the treatment of snoring. However, most published data are based on relatively short-term follow-up results. Anecdotal cases of late recurrence of snoring after an initially successful surgical result have been reported but few formal studies have been performed to determine the true magnitude of this problem. We compared the short-term and long-term results on our patients and found the late recurrence rate after a minimum follow-up period of 12 months (range: 12-84 months, mean 31.3 months) to be in the region of 13%. The risk of recurrence was directly related to the body mass index.
7788931
Bone-anchored hearing aids in patients with sensorineural hearing loss and persistent otitis externa.
Recently, a new bone-conduction hearing aid has become available which can be connected percutaneously to the skull: the bone-anchored hearing aid or BAHA. Several clinical trials have shown its efficacy in patients with a conductive or mixed hearing loss. A second group of potential candidates are patients who suffer from an almost instantaneous skin reaction to any kind of earmould. Three such patients with a predominant sensorineural hearing loss were fitted with a BAHA. The aided free-field thresholds proved to be poor compared with the desired values using prescriptive rules. Speech recognition measured objectively (with tests) and subjectively (with a questionnaire) was comparable or better than with conventional bone-conduction hearing aids. Two patients were using their BAHA all day, whereas the third patient was only using it for a few hours per day. Although it did not produce optimal results, the BAHA seems to be the best solution for these patients.
7788932
A 3-D finite element analysis of the natural frequencies of vibration of a stapes prosthesis replacement reconstruction of the middle ear.
In this work, the natural frequencies of vibration of two different stapes prosthesis replacement reconstructions have been analysed using the finite element method. Prosthesis 1 was constructed of fine stainless steel wire and a Teflon base, while prosthesis 2 was made entirely of Teflon. The results have indicated that generally, the first natural frequency of vibration falls as the prostheses become larger and more bulky. However, the fall in the first natural for prosthesis 1 was modest when compared with that of the isolated tympanic membrane. An important variable influencing frequencies and mode of vibration of the reconstruction was the tightness of fit of the prostheses within the remaining ossicular chain. The tightness of fit in this work was modelled as a range of spring constants applied at the stapes pseudo footplate, together with a series of joint elements at the incus tip/prosthesis head for the Teflon implant. When these spring constraints were below approximately 10 N/mm, the reconstruction exhibited normal mode 1 vibration behaviour, but at larger spring values, an abnormal mode 1 became established resembling the normal mode 2 vibration characteristics. The formation of new geometries and surfaces following reconstruction, introduces new constraints between umbo and stapes footplate particularly at the natural/artificial interfaces. These unnatural constraints may inhibit and modify the natural movements normally occurring at the stapes footplate leading to abnormal modes of vibration.
7788929
Efficacy of topical corticosteroid powder for nasal polyps: a double-blind, placebo-controlled study of budesonide.
Budesonide has been used for a number of years as a topical nasal corticosteroid in the treatment of nasal allergy and nasal polyps. Recently, a new device for powder insufflation where no constituents or preservatives are included has been developed (Rhinocort Turbuhaler, Astra Draco AB, Sweden). The present investigation was designed in order to study the efficacy of topical budesonide powder as the only treatment of nasal polyps. A total of 126 patients entered the study. The medical history and clinical recordings included symptoms and signs, a semiquantitative test of smell and measurement of nasal expiratory peak flow index. Medication was either 200 or 400 micrograms of budesonide powder b.i.d. or placebo. After 1 month an overall assessment of treatment efficacy was made to determine whether the treatment had been a success or a failure. The results showed a statistically significant improvement of symptoms and signs in the actively treated groups. The increase in expiratory peak flow index was about 60% in the actively treated groups as opposed to 16% in the placebo group. The overall assessment of treatment efficacy showed success in about 82% of actively treated patients as opposed to about 43% in the placebo group. It is concluded that budesonide powder is useful in the treatment of nasal polyps.
7788928
Delay in the diagnosis of oral squamous cell carcinoma.
Delay in diagnosis was recorded prospectively in 167 patients with an oral squamous cell carcinoma. The median total delay was 4 months of which two-thirds was patient delay. The corrected survival did not correlate with the total delay. The patient delay was not significantly correlated with tumour or patient factors and the unreliable nature of patient delay information makes such data clinically unusable. In contrast, the professional delay correlated significantly with some of these factors. The delay was longer for women than for men and the older the patient, the longer the delay. The professional delay was longest in patients with small tumours. Thus, registration of the professional delay provides information to be used to improve the diagnostic efficiency of the health care system.
7788927
Establishment and characterization of a human cell line from a squamous carcinoma of the tongue.
A human squamous carcinoma cell line, PWH-S1, has been established from the metastatic lymph node of a Chinese patient with a squamous cell carcinoma of the tongue. The fibroblast-free culture has been propagated in DMEM supplemented with 10% fetal bovine serum for more than 100 passages. PWH-S1 cells showed anchorage-independent growth in 0.3% agar solution. PWH-S1 cell line exhibited a monolayer growth and loss of contact inhibition. The in vitro doubling time of the PWH-S1 cell line was approximately 28 h. PWH-S1 was tumourigenic after inoculation into nude mice. Karyotype analysis showed the chromosome abnormality with a modal number of 69. Electron microscopy demonstrated poorly differentiated neoplastic cells with some features of squamous cell differentiation. No human papillomavirus (type 6, 11, 16, 18, 31) was detected in the PWH-S1 cell line by the polymerase chain reaction.
7788926
Day case myringoplasty using tragal perichondrium.
Day surgery has an ever-increasing role to play in otology. In this study of myringoplasty, tragal perichondrial grafts were placed permeatally as a day case procedure in 32 patients. These are compared with a control group, matched for age and for the size of their perforations, in whom temporalis fascia was grafted via an endaural or postaural incision. The success rate was 94% in the perichondrial group as compared with 84% in the control group (no significant difference P > 0.05). Day case myringoplasty produced less morbidity for the patients and a 40% reduction in theatre time as well as the more obvious savings resulting from a shorter hospital stay.
7788924
Role of blood doping in the coronary vasoconstrictor response to cocaine.
The mechanism by which cocaine induces myocardial ischemia remains controversial. Most prior studies have postulated that cocaine-induced coronary vasoconstriction limits myocardial oxygen delivery during times of increased myocardial oxygen demand. To determine the contribution of altered myocardial metabolic demands to the coronary vasoconstrictor effects of intravenous cocaine (COC 1 mg/kg), we studied 13 conscious, chronically instrumented dogs in the intact state and with heart rate held constant with atrial pacing in the presence and absence of beta-adrenergic blockade with propranolol (2 mg/kg) to limit the inotropic and chronotropic effects of cocaine on associated increases in myocardial oxygen consumption. In the intact state, COC caused a prompt increase in coronary blood flow (+30 +/- 3%, P < .01) that returned rapidly to baseline within 10 minutes, whereas coronary vascular resistance did not increase significantly (+17 +/- 6%, P < .05) until 15 minutes after COC. Notably, myocardial oxygen consumption increased (+57 +/- 4%, P < .01) to a greater extent than oxygen delivery (+42 +/- 3%, P < .01) during the first 2.5 minutes, requiring increased oxygen extraction (from 75 +/- 1% to 80 +/- 1%, P < .01), although only transiently. Thereafter, enhanced oxygen delivery matched the required oxygen consumption without further need to extract additional oxygen. Surprisingly, the enhanced oxygen delivery associated with COC in conscious dogs did not depend on persistent increases in coronary blood flow but rather was due to enhanced arterial oxygen content (+22 +/- 4%, P < .01) as a result of a significant "blood doping" effect with associated increases in circulating hemoglobin from 12.1 +/- 0.4 to 14.2 +/- 0.6 g/dL (P < .01), which persisted for 60 minutes. The myocardial oxygen requirements associated with COC administration have a significant impact on both the magnitude and the mechanism of the coronary vasoconstrictor effects of COC in conscious dogs. Furthermore, the enhanced myocardial oxygen delivery associated with COC administration is not dependent solely on coronary blood flow responses but is due to a significant "blood doping" effect associated with COC.
7788921
Cardiac allograft survival in mice deficient in intercellular adhesion molecule-1.
Intercellular adhesion molecule-1 (ICAM-1, CD54) is a cell adhesion molecule that interacts with the leukocyte beta 2 integrins, lymphocyte function-associated antigen-1, and macrophage antigen-1. ICAM-1 is postulated to play a key role in several cell-cell interactions that are important in allograft rejection, including antigen presentation, transendothelial migration of leukocytes, and leukocyte-medicated myocyte injury. Mice homozygous for a gene-targeted mutation of ICAM-1 were used in two different cardiac transplant models to further define the role of ICAM-1 in the process of allograft rejection. In the first model, hearts from newborn mice were implanted in the ear pinnae of H-2-incompatible recipients. In the second model, intra-abdominal transplantation by direct vascular anastomosis was performed. Time to rejection was defined by the loss of pulsatile activity assessed by visual inspection in the ear model or by cessation of palpable cardiac impulse in the abdominal model. Allograft survival did not differ significantly between control groups that express normal levels of ICAM-1 and those groups using ICAM-1-deficient mutants as either donors or recipients. Histological examination of rejection of both normal and mutant (ICAM-1-deficient) cardiac allografts revealed similar patterns of infiltration of mononuclear and granulocytic leukocytes and myocyte necrosis. Immunostaining with anti-ICAM-1 antibodies showed ICAM-1-positive infiltrating cells in both mutant (ICAM-1-deficient) and normal allografts, with the graft endothelium negative for ICAM-1 staining in the mutant allografts. The absence of surface expression of ICAM-1 in the donor allograft or recipient is insufficient to produce a significant impact on cardiac allograft survival. This study highlights the need to understand more precisely the mechanism of action whereby monoclonal antibodies to ICAM-1 prolong cardiac allograft survival before new therapeutic strategies based on gene transfer technology or small molecule inhibitors are developed. Mutant mice with targeted mutations in cell adhesion molecules provide powerful tools to study the complex role that cell adhesion molecules play in the cellular interactions between donor graft tissue and the recipient that culminate in graft rejection.
7788922
Angiotensin II type 1 receptor blockade inhibits the expression of immediate-early genes and fibronectin in rat injured artery.
Vascular injury activates various kinds of genes, including proto-oncogenes, growth factors, and extracellular matrix proteins. However, the significance of activation of these genes in neointimal formation is poorly understood. Angiotensin II type 1 (AT1) receptor antagonist is shown to prevent neointimal formation after vascular injury, although the mechanism is unclear. To understand the molecular mechanism of vascular thickening, we examined the effects of AT1 receptor blockade on the gene expression of proto-oncogenes, transforming growth factor-beta 1 (TGF-beta 1), and extracellular matrix proteins after vascular injury. Endothelial denudation of the left common carotid artery in Sprague-Dawley rats was performed with a Fogarty 2F balloon catheter. TCV-116 (10 mg.kg-1.d-1), a selective nonpeptide AT1 receptor antagonist, or vehicle was administered orally to rats from 1 day before to 14 days after balloon injury. Injured left and uninjured right common carotid arteries were removed from rats at 1, 6, and 24 hours and 3, 7, and 14 days after balloon injury. Tissue mRNA levels were measured with Northern blot analysis using specific cDNA probes and corrected for 18S ribosomal RNA value. Arterial mRNAs for c-fos, c-jun, jun B, jun D, and Egr-1 increased significantly at 1 hour after balloon injury and decreased rapidly. At 6 hours, ornithine decarboxylase (ODC) mRNA expression reached the maximal levels. TGF-beta 1 and fibronectin mRNA levels started to increase at 6 hours after injury and remained enhanced until 7 days after injury. On the other hand, collagen types I, III, and IV and laminin mRNA levels were not significantly increased over 7 days. Treatment with TCV-116 significantly inhibited the induction of mRNAs for c-fos, c-jun, Egr-1, ODC, and fibronectin in injured artery, whereas the increase in TGF-beta 1 gene expression after injury was not prevented by TCV-116. Immunohistological studies indicated that TCV-116 decreased not only the intimal thickening but also the amount of these extracellular matrix proteins in the intima. The results indicate that AT1 receptor blockade inhibits the induction of immediate-early genes, ODC, and fibronectin in rat injured artery. Thus, inhibition of intimal thickening by AT1 receptor blockade may be mediated at least in part by suppression of multiple genes related to cell growth and migration in the very early phase after vascular injury.
7788920
Atrial electrogram characteristics in patients with and without atrioventricular nodal reentrant tachycardia.
Multicomponent atrial electrograms and "slow pathway potentials" are helpful in identifying target sites for radiofrequency catheter ablation of the slow pathway in patients with atrioventricular (AV) nodal reentrant tachycardia. The purpose of this study was to compare the atrial electrograms recorded at various locations in the right atrium in patients with and without AV nodal reentrant tachycardia to assess the specificity of multicomponent atrial electrograms and possible slow pathway potentials both for the posteroseptal right atrium and for patients with AV nodal reentrant tachycardia. In 25 patients with AV nodal reentrant tachycardia and 23 control patients without AV nodal reentrant tachycardia or dual AV nodal physiology, atrial electrograms with an AV ratio of < or = 1:2 were recorded at the posteroseptal right atrium near the coronary sinus ostium and in the right atrium near the posterior, lateral, and anterior aspects of the tricuspid annulus. Attempts were made to identify broad, multicomponent, and double atrial electrograms. There were no significant differences between the patients with and without AV nodal reentrant tachycardia in the mean number of deflections in the atrial electrograms or in the mean duration of the atrial electrograms recorded at any of the atrial sites. In all patients, the number of atrial electrogram deflections and the atrial electrogram duration were significantly greater at the posteroseptal position than at the other three atrial sites. The prevalence of potentials with the appearance of slow pathway potentials in the posterior septum was similar in patients with and without AV nodal reentrant tachycardia (68% and 70%, respectively). The prevalence of these potentials was 6% to 25% at the other three atrial sites (P < .005 compared with the posterior septum). The atrial electrogram characteristics that have been found to be useful in identifying effective posteroseptal slow pathway ablation sites in patients with AV nodal reentrant tachycardia are equally prevalent in patients without AV nodal reentrant tachycardia or dual AV nodal physiology. Atrial electrograms in the posteroseptal area are broader and contain more deflections than at other areas in the right atrium, possibly because of conduction properties of the posterior transitional zone that are independent of the presence of AV nodal reentrant tachycardia.
7788919
Electrophysiological manifestations of the excitable gap of slow-fast AV nodal reentrant tachycardia demonstrated by single extrastimulation.
Although AV nodal reentrant tachycardia (AVNRT) is a well-known rhythm disorder, its anatomic substrate and electrophysiological mechanism remain to be defined. Previously, the description of the excitable gap (EG) of AVNRT was based on electrical stimulation performed from sites remote from the reentrant circuit. In the present study, we characterized the EG of AVNRT by atrial extrastimulation close to the putative reentrant circuit in the AV junction. In 16 patients (3 men, 13 women; mean age, 45 +/- 13 years) with inducible slow-fast AVNRT (mean cycle length, 353 +/- 52 ms), single extrastimuli with a 10-ms decrement in the premature coupling interval were delivered from the anterosuperior interatrial septum (fast pathway area) and the posteroinferior interatrial septum (slow pathway area) from late diastole until atrial refractoriness. An EG was considered present when resetting or termination of AVNRT was induced by single atrial extrastimulation. The study showed that the duration of the EG of AVNRT was wide, measuring 121 +/- 56 and 123 +/- 47 ms and occupying 33 +/- 11% and 34 +/- 9% of the tachycardia cycle length during single extrastimulation from the slow pathway area and the fast pathway area, respectively. The resetting pattern most commonly manifested as the sum of the coupling interval and the return cycle being less than a fully compensatory pause (two times the basic tachycardia cycle length). However, patterns equal to and greater than a fully compensatory pause were also observed. Of note, in 2 of the 16 patients, atrial extrastimulation from either the fast or slow pathway area also affected the preceding tachycardia cycle length (HH interval), indicating alteration of the anterograde input. In all patients, the curve derived from plotting the coupling interval of extrastimuli against the return cycle during resetting exhibited an "increasing" pattern. The mode of tachycardia termination usually occurred when the premature atrial impulse was orthodromically blocked in the anterograde slow pathway. The EG of slow-fast AVNRT is relatively wide, as demonstrated by single atrial extrastimulation from the interatrial septum near the AV junction. Overall, the electrophysiological manifestations of the EG of AVNRT are very similar to those described in AV reciprocating tachycardia incorporating an accessory connection. These findings lend further support to the notion that, in humans, AVNRT involves a reentrant mechanism with a wide excitable gap.
7788917
Provocation of hypotension during head-up tilt testing in subjects with no history of syncope or presyncope.
Head-up tilt test is increasingly being used to evaluate patients with syncope. This study was designed to evaluate the specificity of head-up tilt testing using different tilt angles and isoproterenol infusion doses in normal volunteers with no prior history of syncope or presyncope. One hundred fifty volunteers were randomized to two groups of 75 each. In group 1, subjects were further randomized to have head-up tilt testing at a 60, 70, or 80 degree angle at baseline followed by repeat tilt testing during a low-dose isoproterenol infusion that increased the heart rate by an average of 20%. In group 2, after having a baseline head-up tilt test at a 70 degree angle for a maximum of 20 minutes, subjects were randomized to have a repeat tilt table testing at a 70 degree angle during a low-dose, 3 micrograms/min, or 5 micrograms/min isoproterenol infusion. In group 1, syncope or presyncope along with hypotension developed in 2 subjects during the baseline test at 60 and 70 degrees of tilt and in 5 subjects during tilting at 80 degrees. The addition of low-dose isoproterenol reduced the specificity minimally from 92% to 88% at both 60 and 70 degrees of tilt but substantially to 60% at an 80 degrees angle. However, 6 of the 10 subjects with a positive test at an 80 degree angle had an abnormal response after 10 minutes of tilt testing. In group 2, using various isoproterenol doses with tilt table testing at a 70 degree angle, low-dose (mean infusion dose, 1.5 +/- 0.45 microgram/min), 3 micrograms/min, and 5 micrograms/min isoproterenol infusions elicited an abnormal response in 1 (4%), 5 (20%), and 14 (56%) of the subjects, respectively. Using multiple logistic regression analysis, head-up tilt testing at an 80 degree angle (P = .01) or during 3 micrograms/min (P = .02) and 5 micrograms/min isoproterenol infusion rates (P < .001) was the most significant predictor of an abnormal response. Head-up tilt testing at a 60 or 70 degree angle with or without low-dose isoproterenol infusion provides an adequate specificity. Caution is needed, however, in interpreting the results if the head-up tilt test at 80 degrees is extended beyond 10 minutes or if high doses of isoproterenol are used.
7788918
Results of the international study of the implantable pacemaker cardioverter-defibrillator. A comparison of epicardial and endocardial lead systems. The Pacemaker-Cardioverter-Defibrillator Investigators.
The purpose of the present report was to document clinical experience derived from the implantation of 2834 epicardial and endocardial cardioverter-defibrillators (ICDs) in 2807 patients who were followed for almost 1 year and to compare the results obtained with the two systems. Patients in the two groups had similar clinical characteristics. More than half of the patients had a total of almost 50,000 spontaneous ventricular tachyarrhythmias that were terminated with equal success (approximately 98%) by epicardial and endocardial ICDs. Lead dislodgement and pocket infection occurred more often with the endocardial than with the epicardial ICD, whereas perioperative mortality was higher with the epicardial ICD than with the endocardial ICD. Mortality from sudden cardiac death was 1.4% in the epicardial ICD group and 0.6% in the endocardial ICD group at 1 year (P = .069). Overall mortality at 1 year was 12.2% and 6.9% for the epicardial and endocardial groups, respectively (P < .001), reflecting the higher surgical mortality for the epicardial system. The endocardial ICD is as effective as the epicardial ICD but incurs lower perioperative mortality.
7788915
Dissociation between exertional symptoms and circulatory function in patients with heart failure.
Patients with heart failure frequently report exertional dyspnea and fatigue. These symptoms are usually attributed to circulatory dysfunction and therefore are typically treated with cardiovascular medications. Serial assessment of exertional symptoms has also become the principal method used to assess drug efficacy in heart failure. Nevertheless, the relation between exertional symptoms in heart failure and circulatory dysfunction remains uncertain. This study was undertaken to investigate the relation between exertional symptoms, ventilatory and skeletal muscle dysfunction, and circulatory function in patients with heart failure. To this end, 52 ambulatory patients with heart failure underwent hemodynamic monitoring during maximal treadmill exercise testing. During exercise, the severity of dyspnea and fatigue was evaluated on a scale of 6 to 20 (Borg scale). The level of perceived exercise intolerance during daily activities was evaluated with the Minnesota Living With Heart Failure Questionnaire and the Yale Dyspnea-Fatigue Index. Maximal treadmill exercise increased the VO2 to 13.4 +/- 2.8 mL.min-1.kg-1, the dyspnea score to 15.7 +/- 2.3, the fatigue score to 14.8 +/- 3.4, the pulmonary wedge pressure to 28 +/- 11 mm Hg, and the pulmonary artery lactate concentration to 34.5 +/- 16.3 mg/dL and decreased the pulmonary artery hemoglobin oxygen saturation to 30 +/- 9%. The level of perceived dyspnea had no relation to the pulmonary wedge pressure and correlated only minimally with the level of excessive ventilation (r = 39). The level of perceived fatigue correlated only weakly with blood lactate concentration (r = .55). Eleven patients (21%) exhibited a normal cardiac output and wedge pressure < 20 mm Hg during exercise, 22 (42%) exhibited a normal cardiac output but wedge pressure > 20 mm Hg during exercise, and 19 (37%) exhibited reduced cardiac output and wedge pressure > 20 mm Hg during exercise. Despite these markedly different hemodynamic responses, all three groups exhibited similar levels of fatigue and dyspnea at comparable workloads and had comparable total scores for the Minnesota Living With Heart Failure Questionnaire and the Yale Dyspnea-Fatigue Index. There was no relation between the Living With Heart Failure Questionnaire and peak exercise VO2 and only a weak correlation between the Dyspnea-Fatigue Index and peak VO2 (r = .48). The level of exercise intolerance perceived by patients with heart failure has little or no relation to objective measures of circulatory, ventilatory, or metabolic dysfunction during exercise. In patients who report severe exertional symptoms, it may be desirable to directly measure hemodynamic response to exercise to ensure that these symptoms are due to circulatory dysfunction.
7788914
Relation between myocardial fractional flow reserve calculated from coronary pressure measurements and exercise-induced myocardial ischemia.
Myocardial fractional flow reserve (FFRmyo) is a functional index of stenosis severity that can be derived from intracoronary pressure measurements performed during maximal vasodilatation. It is defined as the maximal myocardial perfusion during hyperemia in the presence of a stenosis in the epicardial artery expressed as a fraction of its normal maximal expected value. To determine threshold values of FFRmyo, of hyperemic translesional pressure gradient (delta P(max)), and of resting translesional pressure gradient (delta P(rest)) that are uniformly associated with exercise-induced ischemia, we studied the relation between these pressure-derived indexes and the results of exercise ECG. We studied 60 patients with an isolated lesion in one major epicardial coronary artery, normal left ventricular function, and no left ventricular hypertrophy. Maximal exercise ECG (off anti-ischemic medication) was performed within 6 hours before catheterization. Intracoronary pressure measurements were taken at rest and during hyperemia with a pressure monitoring guide wire. ST-segment depressions at peak exercise (considered abnormal when > or = 0.1 mV) were compared with FFRmyo, delta P(max), and delta P(rest). Thirty-seven patients had an abnormal and 23 patients a normal exercise ECG. A significant linear correlation was found between the magnitude of ST-segment depressions and both FFRmyo and delta P(max) (r = -.75, SEE = 0.53; r = .71, SEE = 0.56). A weaker correlation was noted between ST-segment depressions and delta P(rest) (r = .53, SEE = 0.67). Sensitivity and specificity curves were constructed for the prediction of an abnormal exercise ECG for the three pressure-derived indexes. The values that most accurately predicted an abnormal exercise ECG were 66% for FFRmyo, 31 mm Hg for delta P(max), and 12 mm Hg for delta P(rest). No patient with a FFRmyo value > 72% showed an abnormal exercise ECG. In addition, receiver operating characteristic curves demonstrated a greater accuracy of FFRmyo and of delta P(max) than of delta P(rest) for predicting the results of the exercise ECG. In the present study, cutoff values of FFRmyo and translesional pressure gradients are established from the relation between intracoronary pressure-derived indexes and ECG signs of myocardial ischemia during maximal exercise. These values can be helpful for clinical decision making in cases with dubious angiographic results. Furthermore, our data support the concept that stenosis physiology is better reflected by hyperemic than by basal measurements.
7788913
Fibrinogen after coronary angioplasty as a risk factor for restenosis.
Fibrinogen is a risk factor for cardiovascular disease and is related to the severity of coronary atherosclerosis. Its role in restenosis after coronary angioplasty remains unknown. Although platelets and thrombosis contribute to the pathogenesis of restenosis, few clinical data are available concerning the relations between restenosis and proteins of the coagulation and fibrinolytic systems. In 107 consecutive patients undergoing coronary angioplasty, we measured plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, and fibrinogen before and immediately after angioplasty and at a 6-month follow-up. The individual changes of intraluminal diameter were measured by quantitative coronary angiography, and patients were classified according to four definitions of restenosis: (1) a final stenosis > 50%, (2) a loss of minimal luminal diameter during the follow-up period greater than the measurement variability in our laboratory (> 0.52 mm), (3) a loss of at least 50% of the gain in luminal diameter achieved by angioplasty, and (4) the combination of definitions 1 and 2. The relations between coagulation variables and each definition of restenosis were assessed univariately; then with the clinical variables included, the relations were analyzed multivariately. Angiographic follow-up was obtained in 92% of patients with a primary success of angioplasty. Global restenosis rates were 38%, 43%, 48%, and 30% for definitions 1 through 4, respectively. Plasma levels of t-PA antigen and PAI-1 antigen were not associated with any of the four definitions of restenosis. Multivariate analysis demonstrated that von Willebrand factor measured immediately after angioplasty predicted restenosis according to definitions 2 and 3. Fibrinogen measured within 6 months of follow-up was significantly increased in all restenosis groups of the four definitions. Patients with a fibrinogen concentration > 3.5 g/L at follow-up had higher restenosis rates than patients with a concentration < 3.5 g/L: 55% versus 22% (P = .001), 68% versus 31% (P = .002), 63% versus 37% (P = .01), and 74% versus 26% (P = .002) for definitions 1 through 4, respectively. The loss index was lower (P = .003) and the net gain higher (P = .03) in patients with a fibrinogen level < 3.5 g/L. There was a significant correlation between fibrinogen level and angiographic loss index (r = .41; P < .0001). Multivariate analysis confirmed that the fibrinogen level predicted restenosis with all definitions. An independent relation exists between von Willebrand factor measured immediately after angioplasty and restenosis defined by the degree of intraluminal renarrowing. An elevated fibrinogen level during follow-up is a strong biochemical predictor of restenosis. Therefore, fibrinogen should be considered at least as an independent marker of restenosis and perhaps as a common risk factor for both spontaneous coronary atherosclerosis and postangioplasty restenosis, which is an accelerated form of atherosclerosis.
7788912
17 beta-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease.
Women are protected from coronary artery disease until the menopause. Ovarian hormones are vasoactive substances that influence both hemodynamic parameters and atheroma formation. Intravenous ethinyl estradiol has been shown to reverse acetylcholine-induced vasoconstriction in cynomolgus monkeys and humans, and 17 beta-estradiol improves exercise-induced myocardial ischemia in female patients. We investigated the effect of the naturally occurring estrogen 17 beta-estradiol on the coronary circulation in postmenopausal women and men with coronary artery disease. We studied nine postmenopausal women 59 +/- 3 years old, mean +/- SEM, and seven men 52 +/- 4 years old with proven coronary artery disease. They underwent measurement of coronary artery diameter and coronary blood flow after intracoronary infusion of acetylcholine 1.6 and 16 micrograms/min before and 20 minutes after intracoronary administration of 2.5 micrograms of 17 beta-estradiol into atherosclerotic, nonstenotic coronary arteries. Changes in coronary artery diameter were measured by quantitative angiography, and changes in coronary blood flow were measured with an intracoronary Doppler catheter. In female patients, acetylcholine 1.6 and 16 micrograms/min caused constriction before the administration of 17 beta-estradiol (-6 +/- 2% and -8 +/- 5%, respectively, compared with baseline). This constrictor response was converted to dilatation after intracoronary administration of 17 beta-estradiol (+8 +/- 2% and +9 +/- 3%, respectively; P < .01 before versus after estrogen). Acetylcholine 1.6 and 16 micrograms/min increased coronary blood flow before and after the infusion of 17 beta-estradiol. However, the mean acetylcholine-induced increases in coronary flow were significantly greater (P < .009) after (126 +/- 37% and 248 +/- 89%, respectively) than before (94 +/- 31% and 143 +/- 49% mL/min, respectively) the administration of 17 beta-estradiol. 17 beta-Estradiol alone had no significant effect on coronary diameter or coronary blood flow (P > .05). Isosorbide dinitrate (1 mg) caused dilatation of the coronary arteries by 11 +/- 2% (P < .005). In men, acetylcholine 1.6 and 16 micrograms/min caused constriction both before and after the administration of 17 beta-estradiol and caused similar increases in coronary blood flow both before and after the intracoronary administration of 17 beta-estradiol. Infusion of intracoronary placebo in six female control patients 55 +/- 3 years old and six male control patients 56 +/- 3 years old did not change coronary diameter responses or coronary blood flow responses to acetylcholine. 17 beta-Estradiol modulates acetylcholine-induced coronary artery responses of female but not male atherosclerotic coronary arteries in vivo. These human data confirm reports from studies in cynomolgus monkeys that estrogen modulates the responses of atherosclerotic coronary arteries. An enhancement of endothelium-dependent relaxation by natural estrogen (as used in most hormone replacement therapy) may be important in postmenopausal women with established coronary heart disease and may contribute to the acute effect of 17 beta-estradiol on blood flow and its long-term protective effect on the development of coronary artery disease.
7788910
Quantitative measurements of cardiac phosphorus metabolites in coronary artery disease by 31P magnetic resonance spectroscopy.
31P metabolite measurements in the human heart by magnetic resonance spectroscopy (MRS) have been reported previously. By use of a method in which metabolite content was quantified with reference to a standard located outside the chest, it has become possible to measure the content of phosphocreatine (PCr) and ATP in vivo in the human heart. In this study, PCr and ATP contents were measured by 31P MRS and compared in human myocardium with reversible ischemia or scar diagnosed by exercise thallium scintigraphy. Forty-one subjects with stenosis of the left anterior descending coronary artery (> 50%) and 11 healthy control subjects (C) composed the present study group. Patients were divided into two groups on the basis of exercise 201Tl scintigraphy: a reversible 201Tl defect group (RD[+], n = 29) who demonstrated redistribution at late image and a fixed 201Tl defect group (RD[-], n = 12). While the subjects lay supine within the magnet, 31P MR spectra were obtained from the anterior and apical regions of the left ventricle by slice-selected one-dimensional chemical shift imaging. For metabolite quantification, a standard was placed at the center of the surface coil. ANOVA revealed significant differences among the three groups with respect to the mean (+/- SD) PCr at rest (C, 12.14 +/- 4.25 > RD[+], 7.64 +/- 3.00 > RD[-], 3.94 +/- 2.21 mumol/g wet heart tissue, P < .05) as well as a significant decrease in ATP in the RD(-) group (C, 7.72 +/- 2.97; RD[+], 6.35 +/- 3.17 > RD[-], 4.35 +/- 1.52 mumol/g wet heart tissue, P < .05). Compared with healthy control subjects, PCr content decreased significantly in patients with both reversible and fixed 201Tl defects, and ATP content decreased significantly in subjects with fixed thallium defects. These results suggest that the measurement of ATP content in the human heart by 31P MRS is a clinically important method for the evaluation of myocardial viability.
7788908
Genetic approaches to cardiovascular disease. Supravalvular aortic stenosis, Williams syndrome, and long-QT syndrome.
Although family history can be an important risk factor for cardiovascular disease, relatively little is known about the nature of specific genetic risk factors. One approach to this problem is to identify and characterize genes responsible for inherited disorders in the hope that this information will also provide mechanistic insight into common forms of cardiovascular disease. Over the last decade, it has become possible to identify genes that cause human disease by use of the techniques of molecular genetics, specifically genetic linkage analysis, positional cloning, and mutational analyses. We have used these techniques to study three inherited cardiovascular disorders: supravalvular aortic stenosis, Williams syndrome, and long-QT syndrome. We have discovered that the vascular pathology of supravalvular aortic stenosis and Williams syndrome results from mutations involving the elastin gene on chromosome 7q11.23. These mutations include intragenic deletions, translocations, and complete deletion of the elastin gene, suggesting that a quantitative reduction in elastin during vascular development is pathogenically important. To date, only the elastin gene has proved important for supravalvular aortic stenosis. By contrast, genetic linkage analyses in families with long-QT syndrome indicate that at least four distinct genes can cause this disorder. We have identified three LQT loci: LQT1 on chromosome 11p15.5, LQT2 on 7q35-36, and LQT3 on 3p21-24. Recently, we demonstrated that mutations in a putative cardiac potassium channel gene, HERG, are responsible for the chromosome 7-linked form of long-QT syndrome, whereas mutations in the cardiac sodium channel gene SCN5A cause the chromosome 3-linked form of this disorder. HERG mutations and potassium channel biophysics suggest a dominant-negative molecular mechanism and reduced repolarization currents. By contrast, SCN5A mutations probably cause subtle alterations of cardiac sodium channel function and prolonged depolarizing currents. Molecular genetic analyses of long-QT syndrome, supravalvular aortic stenosis, and Williams syndrome have begun to unravel the mechanisms underlying these inherited disorders. Rapid genetic testing for Williams syndrome is now available using a simple cytogenetic test, fluorescence in situ hybridization, but additional work will be required for long-QT syndrome and autosomal-dominant supravalvular aortic stenosis. Improved diagnosis and mechanistic understanding of these disorders should lead to rational treatment and prevention.
7788907
Effects of load manipulations, heart rate, and contractility on left ventricular apical rotation. An experimental study in anesthetized dogs.
Left ventricular twist or torsion has been defined as the counterclockwise rotation of the ventricular apex with respect to the base during systole. We have recently shown that since base rotation is minimal, measurement of apex rotation reflects the dynamics of left ventricular (LV) twist. Since the mechanisms by which load and contractility affect twist are controversial, we aimed to determine the relation between apex rotation and volume, contractility, and heart rate under conditions in which dimensions and pressures were accurately measured. Using our optical device coupled to the LV apex, apex rotation was recorded simultaneously with LV pressure, ECG, LV segment length, and minor-axis diameters (sonomicrometry) in 12 open-chest dogs. Using vena caval occlusion and volume loading, a linear end-diastolic (ED) relation between apex rotation and LV area index was obtained (slope, 0.61 +/- 0.06 degrees/percent change; intercept, -60.1 +/- 6.2 degrees; n = 10) that differed from the end-systolic (ES) relation (slope, 1.36 +/- 0.27 degree/percent change; intercept, -132.5 +/- 24.9 degrees; P < .005). With changes in contractility, afterload, or heart rate, for both ED and ES the apex rotation-volume points fell within the range of the relations established by changing preload, suggesting that volume is the major determinant of twist. Vena caval occlusion (preload and afterload decrease) caused an increase in amplitude of apex rotation, with maximal apex rotation occurring earlier in ejection. In contrast, acute volume loading (predominant preload increase) caused a small decrease in the amplitude of apex rotation, and twist relaxation was delayed into the isovolumic relaxation period. Likewise, with single-beat aortic occlusion (increased afterload), there was a slight decrease in the amplitude of apex rotation, and maximal apex rotation was delayed into the isovolumic relaxation period. Paired pacing (increased contractility) increased the total amplitude of apex rotation by 42% and caused a delay in untwisting until the end of the isovolumic relaxation period. An increase in heart rate over 150 beats per minute resulted in a significant decrease in the amplitude of apex rotation with a similar delay of twist relaxation into the isovolumic relaxation period. The effects of load, contractility, and heart rate manipulations on LV twist as measured throughout the cardiac cycle by the optical apex rotation method are manifested by changes in both the amplitude and dynamics of torsion. LV twist at ED and ES is primarily a function of volume; this relation appears to be unaltered by heart rate, afterload, and contractility. Whereas decreased load caused early untwisting, increases in preload, afterload, heart rate, and contractility caused a consistent pattern of delay in twist relaxation.
7788906
Heterogeneities in [K+]o and TQ potential and the inducibility of ventricular fibrillation during acute regional ischemia in the isolated perfused porcine heart.
The relation between the inducibility of ventricular fibrillation (VF) and heterogeneity of the extracellular potassium concentration ([K+]o) and of TQ potential is unknown. Data from 78 epicardial DC electrodes or from up to 32 intramural K+ electrodes were acquired simultaneously. Induction of VF was attempted with one or two ventricular premature beats induced in normal myocardium in isolated porcine hearts during (1) regional perfusion of the left anterior descending artery (LAD) with a normoxic, hyperkalemic solution ([K+] 6 to 19.6 mmol/L), (2) simulated ischemia, ie, LAD perfusion with a glucose-free, hypoxic solution ([K+] 4 to 16 mmol/L, PO2 < 5 mm Hg, pH 6.98), and (3) regional ischemia produced by stopping LAD flow. During normoxic, hyperkalemic LAD perfusion, no VF could be induced (12 interventions, 7 hearts). During simulated ischemia (27 interventions), VF could be induced only when [K+]o was between 8 and 13.5 mmol/L. After 5 minutes of true regional ischemia, more sites with [K+]o between 8 and 13.5 mmol/L were present than after 10 minutes. VF could be induced with 1 ventricular premature beat in 11 of 17 interventions after 5 minutes and in 0 of 14 interventions after 10 minutes of ischemia (P < .001). Regional simulated ischemia presents a relatively homogeneous condition compared with 5 minutes of regional ischemia (SD +/- SEM of TQ potential in LAD tissue, 0.9 +/- 0.05 versus 2.1 +/- 0.13 mV, respectively). True ischemia superimposed on regional simulated ischemia caused the rapid development of heterogeneities in [K+]o and TQ potential and caused VF after 45 +/- 7 seconds in all interventions. Activation maps of induction of VF suggest a different mechanism of unidirectional block during simulated ischemia from that in true ischemia. (1) In the presence of hypoxia and acidosis, [K+]o between 8 and 13.5 mmol/L provides the conditions necessary for the induction of VF; (2) after 5 minutes of ischemia, these conditions are present in a larger area and inducibility of VF is higher than after 10 minutes of ischemia; and (3) small heterogeneities within the intermediate K(+)-concentration domain (8 to 13.5 mmol/L) are associated with high inducibility of VF.
7788905
Role of endothelin-1 in beagles with dehydromonocrotaline-induced pulmonary hypertension.
Although plasma levels of endothelin-1 (ET-1) increase in patients with pulmonary hypertension (PH), its role in PH is unknown. We investigated the contribution of endogenous ET-1 to cardiopulmonary changes in beagles with dehydromonocrotaline (DMCT)-induced PH. Eight 3-month-old beagles were given a single injection of 3 mg/kg DMCT via the right atrium. During the 8 weeks after injection, the mean pulmonary arterial pressure (PAP) and plasma ET-1 level increased significantly from 11.6 +/- 2.3 to 35.9 +/- 7.1 mm Hg and from 1.24 +/- 0.25 to 3.25 +/- 0.94 pg/mL, respectively. In controls, ET-1 infusion elevated the systemic arterial pressure (SAP) but did not alter PAP. In PH beagles, ET-1 infusion increased SAP, which was attenuated by FR139317 (an endothelin type [ET] A receptor antagonist), and produced a dose-dependent decrease in PAP, which was attenuated by RES-701-1 (an ETB receptor antagonist). In PH beagles, FR139317 infusion decreased PAP, and RES-701-1 infusion increased PAP. Sarafotoxin S6c (an ETB agonist) infusion decreased PAP in PH beagles. These results suggest that endogenous ET-1 is elevated in PH disease and may mitigate PH by acting on ETB receptors.
7788904
Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle cells. Synergistic interaction with hypoxia.
Vascular endothelial growth factor (VEGF) is a hypoxia-inducible direct angiogenic factor. Upregulation of VEGF is thought to mediate many of the angiogenic effects of growth factors that are not direct endothelial cell mitogens. Like VEGF, basic fibroblast growth factor (bFGF) is considered to induce angiogenesis by a direct effect on endothelial cells. This study investigated the possibility that bFGF may also act indirectly by regulating VEGF expression in vascular smooth muscle cells (VSMCs). Incubation of confluent and quiescent cultures of rabbit VSMCs with bFGF caused a time- and concentration-dependent increase in steady-state levels of VEGF mRNA, as analyzed by Northern blot hybridization. Exposure of VSMCs to a threshold hypoxic stimulus (2.5% O2) caused a modest increase in VEGF mRNA levels. However, the combination of 2.5% O2 with bFGF had a marked synergistic effect. This effect was specific for VEGF as hypoxia did not enhance bFGF-induced expression of the proto-oncogene c-myc. Synergistic upregulation of VEGF mRNA expression also was observed between hypoxia and TGF-beta 1. These results suggest that bFGF may promote angiogenesis both by a direct effect on endothelial cells and also indirectly by the upregulation of VEGF in VSMCs. The synergy demonstrated between hypoxia and either bFGF or TGF-beta 1 suggests that multiple diverse stimuli may interact via the upregulation of VEGF expression in VSMCs to amplify the angiogenic response.