Spiral CT: decreased spatial resolution in vivo due to broadening of section-sensitivity profile. Comparable conventional and spiral computed tomographic (CT) scanning protocols for transaxial (n = 30) and multiplanar reformation (MPR) (n = 15) imaging were performed to image the adrenal gland and the upper pole of the right kidney in the same patient, without use of intravenously administered contrast media. The sharpness of soft-tissue-fat interfaces oriented in the transverse (xy) and longitudinal (z) directions was measured as the maximum and full width at half maximum (FWHM) of the edge attenuation profile first derivative. Edge sharpness was qualitatively assessed by three blinded reviewers, who used a four-point scale. In vivo transaxial CT studies showed that the conventional scans produced slightly sharper edges than the spiral scans (mean difference of spiral and conventional FWHM = 0.30 mm [P < .05] [in z direction] and 0.21 mm [P < .05] [in xy direction]). In vivo MPR studies showed that interfaces in the xy plane were significantly less sharp with spiral scanning, whereas interfaces in the z direction were equivalent for conventional and spiral scanning (mean difference of spiral and conventional FWHM = 0.03 mm [P > .05] [in z direction] and 1.19 mm [P < .05] [in xy direction]). Significant respiratory misregistration was present on seven of 15 (47%) conventional MPR scans and on no spiral MPR scans.


Increasing contrast when viewing radiographic images. Illuminating a developed photographic film with parallel or nearly parallel light provides increased contrast compared with the contrast obtained with diffuse incident light. The viewer of radiographic images can obtain increased contrast simply by increasing the distance between the view box and the radiograph, since this results in more parallel incident light. The authors found a contrast increase of more than 40% when x-ray film was positioned 4 m from a view box. Tilting the film relative to the surface plane of the view box gave additional contrast increase at the cost of somewhat distorted geometry. The photographic effects involved deserve a more thorough discussion in textbooks of radiologic and radiographic physics.


Spleen: dynamic enhancement patterns on gradient-echo MR images enhanced with gadopentetate dimeglumine. To examine the pattern of immediate enhancement with gadopentetate dimeglumine on dynamic magnetic resonance (MR) images of the spleen, this study was divided into two parts: In the first part, the authors retrospectively reviewed the dynamic MR images obtained with a fast low-angle shot (FLASH) sequence in the abdomen immediately after injection of gadopentetate dimeglumine in 137 patients. In the second part, dynamic gadolinium-enhanced FLASH images were prospectively compared with contrast material-enhanced computed tomographic (CT) scans in 17 patients with focal splenic lesions discovered on CT scans. In the first part, 108 patients (79%) had an arciform pattern of contrast enhancement; 22 patients (16%), a uniform pattern of high signal intensity; and seven patients (5%), a uniform pattern of low signal intensity. Most patients had arciform enhancement of the spleen; uniform enhancement occurred in some patients with underlying malignant or inflammatory disease. In the second part, all focal lesions seen on CT scans were seen on dynamic MR images (75 lesions), significantly more than were seen on FLASH images (15 lesions) (P < .001).


Gastroesophageal reflux disease: correlation of esophageal pH testing and radiographic findings. In an attempt to ascertain radiologic efficacy in patients with evidence of gastroesophageal reflux disease (GERD) at pH testing, radiographic findings were correlated with pH values obtained with an esophageal monitor worn for a 24-hour period in 112 patients. Fifteen (30%) of 50 patients with abnormal pH test results had esophagitis diagnosed radiographically, compared with six (10%) of 62 with normal pH test results (P < .05). The severity of abnormal pH monitoring results was classified but did not correlate significantly with the prevalence of esophagitis diagnosed radiographically. Hiatal hernia was also more common (80% vs 60%) in patients with abnormal pH test results (40 of 50 patients) than in those with normal results (37 of 62 patients) (P < .05). Pharyngeal, laryngeal, and pulmonary symptoms were common indications for evaluation, and 14 of 27 (52%) patients with hoarseness had an abnormal pH tracing. Only a minority of patients with evidence of GERD as defined by abnormal pH test results had reflux esophagitis diagnosed radiographically.


Esophageal motor disorders: videofluoroscopic and manometric evaluation--prospective study in 88 symptomatic patients. Esophageal motor disorders are best evaluated with manometry, which, however, is time-consuming and not generally available. The authors prospectively investigated the yield of videofluoroscopy in detection of esophageal motor disorders in comparison with that of manometry. Eighty-eight patients with dysphagia, globus sensation, noncardiac chest pain, or progressive systemic sclerosis underwent both manometry and videofluoroscopy at 0-32-day intervals. Videofluoroscopy was performed with one swallowing study in the upright position and up to three swallowing studies in the prone oblique position. Manometric diagnoses of achalasia (n = 15), diffuse esophageal spasm (n = 1), nonspecific esophageal motor disorders (n = 44), and adynamic esophagus (n = 9) were made. Videofluoroscopically, 87% of the patients with achalasia, the one patient with diffuse spasms, 73% of the patients with nonspecific esophageal motor disorders, and all of the patients with adynamic esophagus received a correct diagnosis, for an overall sensitivity of 80%. The radiographic specificity was 79%. The authors conclude that videofluoroscopy is a valuable and reasonably sensitive technique for screening for esophageal motor disorders.


Intraoperative bile duct sonography during laparoscopic cholecystectomy: experience with a 12.5-MHz catheter-based US probe. During elective laparoscopic cholecystectomy, 20 patients underwent intraoperative evaluation of the biliary tract with a commercial 6.2-F, 12.5-MHz catheter-based ultrasound (US) probe. The study tested the feasibility of this technology for mapping the anatomy of the hepatoduodenal ligament and Calot triangle, assessing bile duct integrity, and detecting choledocholithiasis. The duct was studied with a transmural approach, the catheter being placed parallel to, but remaining outside, the bile duct. The common hepatic duct and common bile duct in the vicinity of the cystic duct were seen in all 20 patients; the junction of the cystic duct with the common hepatic duct was seen in nine patients (45%). After the cystic duct was clamped, no sonographic evidence to suggest bile duct injury was noted in any patient. The transmural imaging approach was tested in four pigs in whose common bile duct a single human calculus had been placed. In all instances the size and location of the calculus were accurately detected. Intraoperative US with a catheter-based system is a safe and effective means for interrogation of the extrahepatic biliary tree during laparoscopic cholecystectomy.


Inverted papilloma: evaluation with MR imaging. The authors examined the magnetic resonance (MR) appearance of inverted papillomas to determine if this histologically benign lesion could be distinguished from malignancies of the sinonasal cavity. MR images in 10 patients with histologically proved inverted papilloma were retrospectively reviewed. The signal intensity of inverted papillomas on short repetition time (TR) images was iso- to slightly hypertintense to muscle in all 10 patients. Inverted papillomas had intermediate signal intensity on the long TR/echo time (TE) images. The tumors were iso- or slightly hypointense to fat on long TR/short TE images. In the seven patients who received gadopentetate dimeglumine, all inverted papillomas showed solid inhomogeneous enhancement. A review of eight sinonasal malignancies showed no distinctive signal intensity or enhancement characteristics to help differentiate inverted papillomas from various malignant tumors. The authors conclude that there is no signature MR appearance for the benign inverted papilloma. The main utility of MR imaging is in defining the extent of the lesion.


Intraorbital wood foreign body mimicking air at CT. Computed tomography (CT) revealed a 2-cm linear area of extremely low attenuation in the left orbit of a boy who had been poked in the eye with a tree branch. The appearance and attenuation of the area suggested air, so a diagnosis of orbital emphysema was initially considered. Further research indicated that wood mimics the CT attenuation and appearance of air. A wood splinter was surgically removed from the orbit.


CT of 338 active professional boxers.

CT of 338 active professional boxers. Computed tomography (CT) was performed in 338 active professional boxers. CT scans were abnormal in 25 boxers (7%). The most common CT abnormality was brain atrophy (22 cases). Focal lesions of low attenuation consistent with posttraumatic encephalomalacia were noted in only three boxers. Boxers with abnormal CT scans did not differ from those with borderline or normal CT scans in regard to age, win-loss record, number of bouts, or history of an abnormal electroencephalogram. Thirty-seven boxers with borderline CT scans (49%) and 17 with abnormal CT scans (68%) reported a previous technical knockout (TKO) or knockout (KO), compared with only 89 (37%) of the 238 boxers with normal CT scans (P < .01). Brain atrophy was noted more frequently in boxers with a large cavum septum pellucidum (CSP) than in those with a small or no CSP (P < .05). Boxers with abnormal or borderline CT scans who experienced a TKO or KO were slightly older than those with normal CT scans and a history of a TKO or KO (P < .05).


Common carotid artery bifurcation: evaluation with spiral CT. Work in progress. To determine the utility of spiral computed tomography (CT) in evaluation of carotid artery stenosis, spiral CT images of 20 patients were compared with images obtained with conventional angiography (20 patients), ultrasound (US) (15 patients), and magnetic resonance (MR) angiography (six patients). The category of stenosis was determined for each internal carotid artery on the basis of the percentage of narrowing: mild = less than 30%, moderate = 30%-69%, and severe = 70%-99%. Occlusions were also noted. The degree of carotid stenosis determined with spiral CT correlated with that determined with conventional angiography in 92% of cases, with that determined with US in 97% of cases, and with that determined with MR angiography in 100% of cases. Calcifications and large ulcers were also well delineated. Spiral CT provided an accurate anatomic depiction of the carotid bifurcation, which could be helpful in preoperative evaluation. The major disadvantage of the technique was the need to postprocess data to remove veins, calcifications, and bone structures from the images.


Pituitary adenomas: findings of postoperative MR imaging. Preoperative and postoperative magnetic resonance (MR) images obtained in 25 patients with pituitary macroadenomas (1.1-5.2 cm in diameter) were evaluated to determine normal (physiologic) and abnormal findings after transsphenoidal or subfrontal surgery. With a 1.5-T unit, T1-weighted sagittal and coronal images were obtained before and after administration of gadopentetate dimeglumine. The physiologic changes after surgery included resorption of packing material and sphenoid sinus opacifications, reexpansion of the pituitary gland, and lowering of the optic chiasm. Implanted gelatin foam appeared as an endosellar, circularly enhancing mass that was seen on follow-up studies to have decreased in size. Muscle-and-fat implants appeared as areas of high signal intensity. In 14 patients, residual tumors were found in the suprasellar (n = 4), retrosellar (n = 3), parasellar (n = 8), and/or endosellar (n = 3) space. Residual tumors were differentiated from implant materials by means of location, characteristic signal intensity, and enhancing pattern, which were identical to those of the corresponding preoperative adenoma in 13 cases (93%). Preoperative studies and clinical information are helpful in the evaluation of postoperative MR imaging examinations.


Intracranial lesion enhancement with gadolinium: T1-weighted spin-echo versus three-dimensional Fourier transform gradient-echo MR imaging. The conspicuity of lesion enhancement with gadopentetate dimeglumine was evaluated subjectively and quantitatively through calculation of contrast-to-noise ratios (C/Ns) on T1-weighted three-dimensional (3D) Fourier transform (FT) gradient-echo (GRE) and two-dimensional (2D) FT spin-echo (SE) images of the brain in 406 consecutive patients. One hundred one enhancing intracranial lesions were present in 61 patients, including intra-(n = 76) and extraaxial (n = 25) processes of neoplastic (n = 68), infectious or inflammatory (n = 13), ischemic (n = 11), or vascular (n = 9) origin. Enhancement was apparent in all lesions on 2DFT SE and 3DFT GRE images, with similar subjective conspicuity in 86.8% (87 of 101) of lesions. Quantitative C/N measurements for 2DFT SE (mean, 17.6) and 3DFT GRE (mean, 17.2) imaging were not significantly different (P = .72). These findings, along with the other advantages of 3DFT GRE imaging, indicate that 3DFT GRE examinations are likely to play a major role in the performance of contrast-enhanced MR imaging of the brain.


Basal ganglial signal intensity alterations: reversal after discontinuation of parenteral manganese administration. The authors describe magnetic resonance (MR) imaging findings in a patient receiving long-term total parenteral nutrition (TPN) therapy in whom parenteral manganese administration was experimentally discontinued. MR imaging performed while the patient was receiving standard TPN solution demonstrated marked hyperintensity of the globi pallidi on T1-weighted images. Following cessation of parenteral manganese administration for 1 year, repeat MR imaging demonstrated regression of the abnormal signal intensity.


Human focal cerebral ischemia: evaluation of brain pH and energy metabolism with P-31 NMR spectroscopy. The authors investigated early human focal ischemia with phosphorus-31 nuclear magnetic resonance spectroscopy at 1.89 T to characterize the temporal evolution and relationship of brain pH and phosphate energy metabolism. Data from 65 symptomatic patients were prospectively studied; none of the patients had had ischemic stroke in the internal carotid artery territory before. Twenty-eight neurologically normal individuals served as control subjects. Serial ischemic brain pH levels indicated a progression from early acidosis to subacute alkalosis. When acidosis was present there was a significant elevation in the relative signal intensity of inorganic phosphate (Pi) and significant reductions in signal intensities of alpha-adenosine triphosphate (ATP) and gamma-ATP compared with those of control subjects. Ischemic brain pH values directly correlated with the relative signal intensity of phosphocreatine (PCr) and the PCr index and inversely correlated with the signal intensity of Pi. There was a general lack of correlation between either ischemic brain pH or phosphate energy metabolism and the initial clinical stroke severity. The data suggest a link between high-energy phosphate metabolism and brain pH, especially during the period of ischemic brain acidosis, and the authors propose that effective acute stroke therapy should be instituted during this period.


Isolated choroid plexus cysts in the second-trimester fetus: is amniocentesis really indicated? Choroid plexus (CP) cysts have been associated with trisomy 18, although most fetuses with CP cysts are normal. Since many fetuses with trisomy 18 have other sonographic abnormalities, the necessity of obtaining a karyotype for all fetuses with isolated CP cysts remains controversial. The authors prospectively studied 234 second-trimester fetuses with sonographically discovered CP cysts. Two hundred twenty of them had no other sonographic findings. None of these 220 normal fetuses had evidence of aneuploidy at amniocentesis or an anomaly at birth. Fourteen fetuses had major anomalies detected in utero: 11 had trisomy 18, one had triploidy, and two had normal karyotypes but were structurally abnormal. While size and bilaterality of the CP cysts were not helpful in predicting aneuploidy, the meticulous anatomic survey of fetuses with CP cysts allowed successful identification of all aneuploid fetuses. These data show that the yield of abnormal karyotypes in fetuses with isolated CP cysts is low and may not justify the risk of amniocentesis.


Appendicitis: usefulness of US in diagnosis in a pediatric population. One hundred eighty pediatric patients with suspected appendicitis were prospectively examined with graded compression ultrasonography (US) to assess the sensitivity, specificity, and accuracy of graded compression US in the diagnosis of appendicitis in children and to compare those results with results of clinical assessment in the diagnosis of this disorder. Patients were assigned to one of three groups prior to US based on the clinical level of confidence that appendicitis was present and on the planned management decision. Of 141 patients in the low- and intermediate-clinical risk categories, 20 (14%) had appendicitis: US had a sensitivity of 100%, specificity of 97%, and accuracy of 97% in these two groups. Of 39 patients in the high-clinical risk category, 32 (82%) had appendicitis: US had a sensitivity of 81%, specificity of 86%, and accuracy of 82%. Of 52 patients with surgically proved appendicitis, the initial management decision was to discharge to home or admit for observation and further testing in 18 (35%). Results at US were positive for appendicitis in all 18 patients in the latter two categories.


Brain abnormalities in male children and adolescents with hemophilia: detection with MR imaging. The Hemophilia Growth and Development Study Group. Cranial magnetic resonance (MR) imaging was performed in 124 male patients (aged 7-19 years), from 14 institutions, in whom a diagnosis of moderate to severe hemophilia was made. Blood tests in all subjects were negative for human immunodeficiency virus. Findings in MR studies were abnormal in 25 (20.2%) subjects. Six lesions in five subjects were classified as congenital. The most commonly identified congenital lesion was a posterior fossa collection of cerebrospinal fluid (five cases). Twenty-two subjects had acquired lesions that were probably related to the hemophilia or its treatment. The most commonly acquired lesions were single- or multifocal areas of high signal intensity within the white matter on T2-weighted images noted in 14 (11.3%) subjects. Two subjects had large focal areas of brain atrophy, and six had some degree of diffuse cerebral cortical atrophy. Three subjects (2.4%) had hemorrhagic lesions. To the authors' knowledge, the unexpected finding of small, focal, nonhemorrhagic white matter lesions has not previously been reported.


Blood flow imaging through detection of temporal variations in magnetization. Two hypotheses were tested: (a) that view-to-view variations in bulk phase and modulus of magnetization in vascular volume elements can indicate the presence of disordered blood flow, and (b) that a substantial loss of signal intensity on magnetic resonance (MR) angiograms of poststenotic regions is due to view-to-view changes in magnetization. To test these hypotheses, a technique was developed in which view-to-view variations in transverse magnetization were used to create angiographic projection images, which showed only disordered flow (disordered flow maps) in vitro and in vivo. In phantom studies, this technique recovered signal intensity downstream from stenoses. A combination of disordered flow maps with morphologic images improved visualization of stenotic regions and provided information on characteristics of local flow. These results show that view-to-view variations in transverse magnetization occur in regions of disordered flow and are an important cause of loss of signal intensity. This technique can provide information about dynamic blood flow and improve depiction of anatomic structures on MR angiograms.


Iliotibial band friction syndrome: MR imaging findings. Six patients with clinical histories and physical examination results consistent with iliotibial band friction syndrome (ITBFS) were examined with magnetic resonance (MR) imaging. Ill-defined decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images was present deep to the iliotibial band, adjacent to the lateral femoral epicondyle. Axial fast imaging with steady-state precession (FISP) gradient-echo sequences were essential in differentiating the ill-defined signal intensity abnormality associated with ITBFS from fluid in the lateral knee joint. None of these patients were found to have lateral meniscal tears, and all responded to conservative measures directed at treating ITBFS. The authors conclude that MR imaging may be useful in confirming or establishing the diagnosis of ITBFS in patients with the appropriate clinical history and distal lateral thigh or lateral knee pain.


Ulnar collateral ligament injury in baseball pitchers: MR imaging evaluation. The ulnar collateral ligament (UCL) provides stability to the medial aspect of the elbow during valgus stress. Trauma to this ligament may result from repetitive forceful throwing. Diagnosis of UCL injury has been based on clinical findings of medial joint pain and valgus instability, as direct imaging of this structure has not been available. Eleven baseball pitchers with clinical evidence of UCL injury were evaluated with magnetic resonance (MR) imaging. Surgical correlation was obtained in six patients, four of whom underwent UCL reconstruction. MR imaging findings in UCL injury included laxity, irregularity, poor definition, and increased signal intensity within and adjacent to the UCL. These findings reflect the presence of hemorrhage and/or edema within the UCL due to repeated microtears, which eventually lead to weakening and possible disruption of the UCL. Optimization of spatial resolution, signal-to-noise ratio, and other technical factors is critical for evaluation of the UCL due to its small size. MR imaging is useful in documenting the presence and severity of injury to the UCL and in distinguishing this entity from other causes of elbow pain.


Menisci of the knee: radial MR imaging correlated with arthroscopy in 259 patients. Similar to arthrograms, radial plane magnetic resonance (MR) images of the knee provide cross-sectional images of the menisci that are perpendicular to the long axis of the meniscus. The authors evaluated 259 consecutive patients who underwent MR imaging of the knee and arthroscopy. Radial multiplanar gradient-recalled-echo imaging was performed--with repetition time of 700 msec, echo times of 12 and 31 msec (700/12, 31), and a flip angle of 20 degrees--as well as sagittal spin-echo imaging (2,500/20, 80). The radial and sagittal images were interpreted separately and then in combination, and findings were compared with arthroscopic reports. There was no statistical difference between the interpretations of the radial and sagittal images in the evaluation of the menisci. When the interpretations of the radial and sagittal images were combined, the sensitivity and specificity improved slightly. The radial images increased the conspicuity of meniscal tears but at the expense of anatomic detail. The sagittal images enabled better evaluation of the meniscocapsular attachment region and some flap tears of the meniscal free edge. The interpretive accuracies of the combination of sagittal and radial images were 92% and 93% for the medial and lateral menisci, respectively.


Diagnosis of soft-tissue masses with MR imaging: can benign masses be differentiated from malignant ones? A blinded, retrospective review of 83 soft-tissue masses (49 benign and 34 malignant) was performed to evaluate the ability to distinguish benign from malignant soft-tissue masses with magnetic resonance (MR) imaging. The correct histologic diagnosis was reached in 31% of cases by one reader and in 16% of cases by the second reader. Mean sensitivity was 50% for benign masses and 80% for malignant masses. The majority of both benign and malignant masses had inhomogeneous signal intensity and at least partially irregular borders. Malignant masses uncommonly had smooth borders and homogeneous signal intensity. MR imaging can be used to evaluate the extent of soft-tissue masses, but most masses will require biopsy to determine if they are benign or malignant.


Osteosarcoma after chemotherapy: evaluation with contrast material-enhanced subtraction MR imaging. A new magnetic resonance (MR) technique, gadolinium-enhanced subtraction MR imaging, was developed to evaluate the response of patients with osteosarcoma to chemotherapy. Ten patients, who had received chemotherapy for osteosarcoma of the lower extremity, underwent MR imaging 3 days before surgery. After routine MR imaging was performed, subtraction MR was performed in the plane in which the tumor was best visualized. With gadopentetate dimeglumine (0.1 mmol per kilogram) on a standard MR console, subtraction images were created by subtracting precontrast images from gadolinium-enhanced T1-weighted images. The time of maximal tumoral vascular uptake was 1 1/2 minutes after injection, and, therefore, the subtracted image obtained at this time was used for evaluation of viable tumor. Independently, radiologists and histopathologists examined their respective studies for viable tumor to differentiate responders from nonresponders. Four of 10 osteosarcomas were classified as good responders because they appeared as nonenhancing masses, with or without enhancing thin lines, or small nodules (< or = 3 mm wide). At histopathologic examination, all were good responders with less than 3% viable tumor. Six of 10 osteosarcomas were classified as nonresponders because they appeared as enhancing high-signal-intensity masses measuring more than 3 mm in width. Five tumors had between 18% and 43% viable tumor cells.


Assessment of whole-body composition with dual-energy x-ray absorptiometry. Dual-energy x-ray absorptiometry (DXA) allows noninvasive direct measurement of the three major components of body composition: lean body mass (LBM), fat body mass (FBM), and bone mineral body mass (BBM). To study the accuracy and short-term and long-term precision of body composition measurements, the authors measured body composition with DXA in 60 healthy young adults. Independent measurement of LBM (LBMK-40), obtained from the determination of the whole-body content of potassium-40 with a whole-body scintillation detector, was highly correlated with LBM determined with DXA (LBMDXA) (LBMK-40 = 1.069.LBMDXA,R2 = .996). Assessment of body composition in 10 patients with acquired immunodeficiency syndrome (AIDS) and 10 patients with cystic fibrosis was performed with DXA. The AIDS patients showed a marked decrease in LBM, while in patients with cystic fibrosis, LBM and BBM were decreased. DXA measurements of body composition appeared accurate and precise enough to be of clinical relevance in detecting specific alterations of body composition.


Subperiosteal resorption: effect of full-frame image compression of hand radiographs on diagnostic accuracy. Image compression is essential to handle a large volume of digital images, including computed tomographic, magnetic resonance, computed radiographic, and digitized images in a digital radiology operation. Developed during the past few years, full-frame bit allocation performed with the cosine transform technique has been proved to be an excellent irreversible image compression method. This article describes the effect, on the accuracy of diagnosis of subperiosteal resorption, of using the hardware compression module to produce hand radiographs. Receiver operating characteristic analysis of the interpretation of 71 radiographs by five observers demonstrated that there is no statistically significant difference in diagnostic accuracy between the original radiographs and compressed and reconstructed images obtained with a compression ratio as high as 20:1.


Expandable intravascular catheter: percutaneous use for endoluminal retrievals. Percutaneous use of an expandable vascular access catheter that can be deployed to temporarily occlude the entry vessel during retrieval of embolic material is described. The catheter was used to facilitate removal of two intraarterial objects, a postangioplasty free atheroma fragment and a displaced Gianturco coil. The expanded catheter end was equal to the arterial lumen, thus preventing distal embolization. The large distal lumen also facilitated plaque or foreign body removal by allowing deployment of various endovascular tools.


CT angiography with spiral CT and maximum intensity projection. The authors describe a technique for obtaining angiographic images by means of spiral computed tomography (CT), preprocessing of reconstructed three-dimensional sections to suppress bone, and maximum intensity projection. The technique has some limitations, but preliminary results in 48 patients have shown excellent anatomic correlation with conventional angiography in studies of the abdomen, the circle of Willis in the brain, and the extracranial carotid arteries. With continued development and evaluation, CT angiography may prove useful as a screening tool or replacement for conventional angiography in some patients.


The left atrial catheter: its uses and complications. The authors describe the radiographic appearance of the left atrial catheter, a widely used postsurgical intracardiac device. Recognition of the characteristic appearance of this catheter should be of value in detection of potential complications, including line fracture with resultant retention and/or embolization, infection, prosthetic valve dysfunction, and even cardiac tamponade.


Goldfish ependymins: cerebrospinal fluid proteins of meningeal origin. Ependymins are unique secretory proteins from the goldfish brain which have calcium binding capacity. They are synthesized in the leptomeninx and appear subsequently as the predominant protein constituents in the cerebrospinal fluid (CSF). In contrast, the serum is nearly devoid of ependymins. The perimeningeal fluid (PMF) between the meninx and the skull represents a mixture of CSF and serum. The different composition of PMF and CSF implies that there is no open communication between these two compartments. Separation is probably achieved by an arachnoid-like meningeal barrier as proposed from ultrastructural studies. This basic CSF system of fish is compared with that of higher vertebrates.


Peptide receptors of the blood-brain barrier and substrate transport into the brain. The BBB is a target for some peptide signals, as demonstrated by our group for arginine-vasopressin (AVP) and atriopeptin (ANP). Peptide molecules contacting the luminal surface of endothelial cells interact with specific high-affinity binding sites. The minimal simple diffusion of peptide molecules across the layer of endothelial cells which are connected by tight junctions is most probably without any significance under physiological conditions, although that question should be checked for brain regions like the olfactory bulb in which some leakiness of the BBB can be demonstrated. The AVP- and ANP-receptors at least partly localized at the luminal surface of the endothelial cells are heterogeneously distributed in the vessels of the brain. The number of AVP receptors is up-regulated by ligand deficiency, which induces furthermore a decrease in the receptor affinity. At physiological concentrations AVP and ANP do not affect the tightness of the BBB, but regulate the transcellular transfer of essential substances from blood to brain. AVP decreases the Km and Vmax of the transporter of large neutral amino acids, and ANP alters the water permeability of the endothelial cell layer. The phenomenon that the cells of the tight epithelium representing the BBB need information from blood-borne peptide signals for the regulation of intercompartmental transport processes seems to be only a special case of a general principle concerning tight epithelial cell layers which separate compartments containing fluids of different composition; amino acid transport across the intestine is regulated by specific peptides contacting that barrier, the casomorphins.


Experimental models of altering the blood-brain barrier. The passage of a substance from blood to brain can be enhanced by altering the permeability of the substance itself or by altering the BBB characteristics. Example of the former is to increase lipid solubility, glycosylation and cationization, liposome entrapment and coupling to carriers. Unselective opening of the BBB can be obtained by a local or systemic increase of the intravascular pressure, by intracarotid injection of hyperosmolar solutions or by substances that alter the endothelial surface charge such as protamine sulphate. Substances that alter the fluidity of membranes can reduce or enhance the permeability of the BBB. In experimental models involving temporary opening of the BBB possible long-term hazardous effects must be considered.


Age-related pathophysiology of the blood-brain barrier in heat stress. The possibility that the blood-brain barrier (BBB) might play an important role in the pathophysiology of heat stress (HS) has been examined in young (age 8-9 weeks) and adult (age 24-32 weeks) rats. Exposure of young rats to 4 h HS at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 47-50%, wind velocity 20-26 cm/sec, simulating the environmental conditions of Varanasi, India, during the month of June) resulted in a marked hyperthermia (41.7 +/- 0.23 degrees C) and behavioral symptoms. In these animals there was a profound increase in the permeability of the BBB to Evans blue-albumin (EBA) (464%) and to 131I-sodium iodide (515%), accompanied by a marked increase in the brain water content (4%), of the levels of serotonin (5-hydroxytryptamine, 5-HT) in plasma (687%) and in brain (267%) and a pronounced reduction (30%) in cerebral blood flow (CBF). Morphological examination using light- and electron-microscopy revealed profound neuronal changes associated with a marked increase in glial fibrillary acidic protein (GFAP) and in vimentin immunoreactivities, together with a substantial reduction in myelin basic protein (MBP) immunostaining in the brain. These changes were more pronounced in the brain-stem reticular formation, pons and medulla region. On the other hand, exposure of adult animals to the same intensity of HS resulted in mild or no changes in BBB permeability, content of brain water and 5-HT in the plasma and brain, CBF or other cellular changes.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of central administration of angiotensin II on cerebrospinal fluid formation in rabbits. The effect of central administration of AII on CSF formation was studied in alpha-chloralose and urethane anesthetized rabbits using the ventriculocisternal perfusion method. AII infused i.c.v. at rates of 5.5 and 55 pg/min significantly decreased CSF production by 25% and 35%, respectively. In contrast, AII when given at 5.5 ng/min did not change CSF formation. It seems that drop in CSF production observed during central administration of AII at low doses is mediated by both increased vasopressin release and activation of the sympathetic nervous system. The lack of changes in CSF formation with the highest AII dose used is not clear at present and awaits further investigation. Specific AII antagonist, saralasin, was found to significantly increase CSF production in four of five animals studied. It is suggested that in normal conditions AII may exert a tonic inhibitory effect on CSF formation.


Density of perfused capillaries in living human brain during functional activation. Recent evidence has indicated that functional activation of cerebral cortex is accompanied by increases of blood flow and glucose consumption but not oxygen consumption. No explanation has been advanced for this change of the flow-metabolism couple. We formulated the hypothesis that oxygen delivery to brain tissue is diffusion-limited by the enormous hemoglobin binding, and rate-limiting for the oxygen consumption of the tissue. One prediction of this hypothesis is very low oxygen tensions in the tissue. A second prediction is the inability of oxygen consumption to increase during functional activation in the absence of recruitment of capillaries for the oxygen diffusion capacity. We designed a study to test the latter prediction by calculating the density of functioning capillaries during vibrotactile stimulation of the parietal cortex. We defined functioning capillaries as capillaries that transport glucose and therefore calculated the capillary density from the glucose diffusion capacity (K1) of the cerebral capillaries. We confirmed the presence of a partial flow-CMRglc couple (2:1) during the functional activation. Oxygen consumption did not change despite an increase of capillary density in proportion to the change of blood flow.


Circumventricular organ capillaries.

Circumventricular organ capillaries. Most circumventricular organs (CVOs) have unusually dense and permeable capillary networks that facilitate secretion of or tissue penetration by circulating substances, unlike other nervous system structures wherein blood-brain barrier (BBB) properties of the capillary endothelium limit solute permeability. In this brief review, I shall discuss new facts from recent experiments, and draw on interpretations from previous studies, to illustrate how capillary systems vary both between and within some CVOs, how closely microvascular properties coincide topographically with the distribution and density of neuropil, transmitter substances and hormonal binding sites, and how physiological data can be combined with morphological descriptions of capillary beds to accent specialized processes of blood-brain solute exchange in individual CVOs. The emphasis of this paper is on exchange microvessels of the rat area postrema (AP), subfornical organ (SFO) and median eminence (ME) which are regions of dense binding for several hormones and contain appreciable numbers of neurons (AP and SFO) or neural terminations that may be part of the sensing apparatus for humoral messengers of homeostatic systems. The work is intended to highlight established concepts about the process of blood monitoring by CVOs, summarize new morphological and physiological characteristics of their capillaries, and provide clues to novel research that could foster further understanding of these curious sentinel and secretory organs of the brain.


Adrenalectomy aggravates ischemic brain edema in female Sprague-Dawley rats with carotid arteries ligated. The effect of adrenalectomy has been investigated in a model of global cerebral ischemia. After bilateral carotid ligation the mortality rate was increased in adrenalectomized rats, and this effect was prevented by glucocorticoid pre-treatment. Adrenalectomy accelerated the appearance of the symptoms of cerebral ischemia, resulting in a moderate aggravation of brain edema and in a significant decrease in the concentration of high-energy phosphate esters. Our findings support the view that endogenous glucocorticoids may play a role in the amelioration of ischemic brain injuries in rats.


Cytochemistry of CSF-contacting neurons and pinealocytes. Gamma aminobutyric acid (GABA)-immunoreactive neurons of the paraventricular organ of the bony fish Coregonus albus send dendrites into the third ventricle. Their axons run to the synaptic zone of the infundibular lobe. The dendrites may take up some chemical information from the third ventricle, while the axons communicate it to the neuropil of the hypothalamus perhaps to modify its activity according to the state of the CSF. Serotonin-immunoreactive CSF-contacting neurons in the spinal cord of the hagfish Myxine glutinosa from dendrite terminals in the central canal and bear stereocilia like known mechanoreceptors. The Reissner's fiber runs above the stereocilia and flows out from the central canal through its caudal opening. Possibly, the fiber keeps open this aperture and ensures the flow of the CSF, which may serve as a mechanoreceptory input for the CSF-contacting neurons. In the pineal recess of hedgehog, CSF-contacting pinealocytes develop enlarged cilia corresponding to the photoreceptor outer segments of submammalian pinealocytes. Potassium pyroantimonate cytochemistry shows a similar localization of calcium ions in the mammalian pinealocyte as in the submammalian photoreceptor ones. Pineal calcifications are present in some birds (goose, duck) and may be connected to the photoreceptory Ca-exchange of the pineal organ. Axonic processes of pinealocytes form synapses on secondary neurons in mammals (hedgehog, rat, cat). Such neurons are also present in human pineals. Axons of these neurons constitute a pinealofugal pathway. In the cat, some of the intrinsic pineal neurons are GABA-immunoreactive, they form axodendritic and axo-axonic synapses (inhibitory?) on immunonegative neurons and pinealocytes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparative ultrastructure and opsin immunocytochemistry of the retina and pineal organ in fish. The pineal organ and retina were compared in developing charr and cisco, further in adult cisco, eel, creek chub, dace, zebrafish and black moli by opsin immunocytochemistry. In prehatching charr embryos, retinal rods and cones and pinealocytes displayed well-developed outer segments and formed synapses. Differentiation of the retina started centrally but was more advanced in the dorso-caudal retina than rostroventrally. The pineal organ differentiated earlier distally than proximally. In the cisco, the pineal organ and retina differentiated around hatching. In charr embryos, further in the larval and adult species studied, opsin immunoreactivity was found in retinal rods, accessory cones and many "rod-like" pinealocytes, a result indicating the presence of rhodopsin and/or porphyropsin. Retinal principle cones, long and short cones and some "cone-like" pinealocytes were opsin-immunonegative; they are thought to represent red- and/or u.v./violet-sensitive elements. The pineal organ may be involved in negative phototaxic behavior. Both the retina and pineal organ appear to be suitably differentiated to detect light in the larval and embryonic charr.


Response of CFU-GM (colony forming units for granulocytes and macrophages) from intact and pinealectomized rat bone marrow to murine recombinant interleukin-3 (rIl-3), recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF) and human recombinant erythropoietin (rEPO). The present study provides evidence, for the first time, of a role of the pineal gland in the proliferation of CFU-GM under the influence of different cytokines. The degree of colony formation in different cytokine groups was evaluated after 24 h, 3, 7 and 10 days. The colony growth in the present type of bone marrow cell cultures slows after the 10th day and ceases after the 14th day of incubation. The results show that rGM-CSF and the combination of rGM-CSF with rIl-3 and with rEPO stimulate the colony formation of granulocytes and macrophages. A 50% general reduction in the colony number was noted in the pinealectomy group. Their pattern of response to the different cytokines was similar to that of the intact group. It is suggested that the pineal activity has a physiological role in important aspects of host defence mechanisms, such as the proliferation of CFU-GM.


Immunocytochemical demonstration of serotonin-immunoreactive cerebrospinal fluid-contacting neurons in the paraventricular organ of pigeons and domestic chickens. The paraventricular organs (PVO) of the pigeon and domestic chicken contain at least three types of serotonin-immunoreactive (serotonin-ir) CSF-contacting neurons. Type 1 neurons were predominant. They had two bipolar extending processes. The somata were mostly found in the pars hypendymalis. Type 2 neurons were characterized by thin and long apical processes. Their perikarya were found in the pars distalis of the PVO or the more lateral area of this organ. Type 3 neurons were considerably smaller and had round somata. They were mostly bipolar with thin and short dendritic processes and thin basal processes. A small number of this type was conspicuous along the cranial peripheral region of the PVO. In addition to the PVO area, aggregations of small, bipolar serotonin-ir CSF-contacting neurons were shown in the most caudal wall of the third ventricle of both species, distributed medially or paramedially. Immunoelectron microscopy revealed many dense granules in apical ventricular processes and perikarya. Synaptic connections were frequently observed on basal processes.


The bovine subcommissural organ: cytochemical and immunochemical characterization of the secretory process. Specific glycoproteins of the bovine subcommissural organ (SCO) were studied by means of various techniques: light and electron microscopy, immunoaffinity chromatography, electrophoresis and Western blotting. Use of lectins (Con A, WGA, PHA-E and -L, LCA) allowed to specify the synthesis and release of complex-type glycoproteins that bear high-mannose-carbohydrate chains in their precursor forms and probably triantennary carbohydrate chains in their mature forms. Antibodies raised against SCO extracts were characterized by means of various tests and used to purify specific compounds. Immunopurified fractions using A99 polyclonal antibody contained numerous polypeptides reactive with Con A, their apparent molecular weight (MW) ranging from 240 to 50 kDa. Only two glycopeptides were strongly labeled with WGA (98 and 52/54 kDa MW). Immunopurified fractions using C1B8A8 monoclonal antibody, specific of the complex-type glycoproteins at different steps of glycosylation, showed three specific Con A-reactive polypeptides at 88, 54 and 34 kDa MW. Only the 34 kDa glycopeptide was strongly labeled with WGA. The latter could correspond to the monomeric form of the secreted compound. Electrophoretical analyses of Reissner's fiber material allowed the detection of a WGA-positive smear in the upper part of the blots, suggesting that the complex-type glycoproteins, when released into the CSF, constitute a stable polymer.


Developmental neuron-glia interactions: role of serotonin innervation upon the differentiation of the ependymocytes of the rat subcommissural organ. The rat subcommissural organ (SCO), which forms the roof of the third ventricle is an adequate model to study certain mechanisms of neuron-glia interactions in vivo. The ependymocytes, the main component of the SCO, have a glial origin. They possess particular phenotypic characteristics: they accumulate [3H]GABA by a specific uptake mechanism, contain transitory GFAP during ontogenesis and do not express PS100; on the other hand they receive a 5HT input which forms typical synaptic contacts. This innervation is of particular interest to approach neuron-glia interactions during the differentiation. Studies of GABA uptake carriers during ontogenesis in SCO ependymocytes show a correlation between the onset of the 5HT innervation and the advent of the GABA uptake. Moreover, destruction of the 5HT innervation by a neurotoxin (5-7-dihydroxytryptamine), before its arrival at the SCO in newborn rat, inhibits the formation of the GABA uptake system and causes the expression of PS100 in adult SCO cells. On the other hand, the SCO of newborn rats transplanted to the fourth ventricle of an adult host rat had no capacity to take up GABA and expressed PS100 3 months after its transplantation. Finally, the SCO ependymocytes of species devoid of 5HT innervation (rabbit, mice) were unable to take up GABA and contain PS100. These data suggest that neuron-glia interactions are necessary for the advent of GABA uptake carriers and can control the expression of glial markers during ontogenesis in SCO ependymocytes.


Drug metabolizing enzymes in the rat pituitary gland. Brain protection against chemicals is mainly provided by the specific properties of cerebral microvessels forming the blood-brain barrier. In addition, several drug metabolizing enzymes have been evidenced both in brain tissue and in cerebral capillaries, suggesting their participation in the enzymatic protection of this organ. The pituitary gland, like true circumventricular organs, lacks a tight vascular endothelium and therefore is especially sensitive to blood-native toxic or pharmacologically active molecules. We report here the presence of cytochrome P-450 in the pituitary gland and its main mitochondrial localization. The O-dealkylase activity measured towards 7-benzoxyresorufin, a substrate for the main cytochrome P-450 isoforms involved in the metabolism of xenobiotics, was 5 times higher in the pituitary gland than in the brain cortex. Similarly, microsomal epoxide hydrolase, which inactivates reactive epoxides to trans diol molecules, and two conjugating enzymes, 1-naphthol UDP-glucuronosyltransferase and glutathione-S-transferase, display respectively 6, 4 and 7 times higher activities in the pituitary gland. 7-Benzoxyresorufin-O-dealkylase, 1-naphthol UDP-glucuronosyltransferase and membrane-bound epoxide hydrolase activities were significantly increased in the pituitary gland as an adaptive response to an in vivo treatment by an exogenous inducer, 3-methylcholanthrene. These results suggest that these enzymatic systems play a role in the protection of the pituitary gland towards drugs or toxic substances.


Efferent neural pathways of the lamina terminalis subserving osmoregulation. Studies in rats and sheep show that neurons in the CVOs of the lamina terminalis provide extensive neural input to the vasopressin-containing cells of the supraoptic nucleus. This input is both by direct pathways and via a synapse in the MnPO which also has projections to the vasopressin-containing cells of the SON. Neurons throughout the lamina terminalis (including possible osmoreceptors in the OVLT and subfornical organ) are activated by systematic hypertonicity. It is likely that in response to hypertonicity they signal the SON and PVN to release vasopressin and elsewhere to elicit other osmoregulatory responses such as thirst and the excretion of sodium.


Functional hypothalamic angiotensin II and catecholamine receptor systems inside and outside the blood-brain barrier. To elucidate the contribution of various hormones and neuromodulators in the central nervous control of body fluid homeostasis, the saltwater-acclimated Pekin duck represents an ideal model due to the cytoarchitecture of its hypothalamus, and the marked systemic and hypothalamic sensitivity of its osmoregulatory system. Employing animal physiology, electrophysiology, histochemistry and receptor binding techniques, the role of angiotensin II (A II) and norepinephrine (NE) as both circulating hormones and neurotransmitters in central osmoregulation through interaction with neuronal targets inside and outside the blood-brain barrier (BBB) could be investigated. Application of both agents into the systemic circulation or into the cerebrospinal fluid of conscious animals, and the monitoring of hypothalamo-neurohypophyseal antidiuretic hormone ADH (= AVT) release, cardiovascular parameters such as mean arterial pressure (MAP) and avian salt gland function allowed to discriminate between actions of A II and NE at sites within or outside the BBB. Of the latter, the median eminence (ME), the subfornical organ (SFO) or the organum vasculosum laminae terminalis (OVLT) are of prime importance. Receptor autoradiography using radioiodinated ligands specific for A II, alpha 1-, alpha 2- and beta-receptors including the pharmacological characterization of these binding sites permit to establish a molecular correlate of the modulatory actions of both A II and NE.


Progressive increases of protein synthesis in the circumventricular organs during chronic dehydration in rats. The quantitative autoradiographic method with L-(35S)methionine was applied to investigate the effect of chronic dehydration on rates of protein synthesis in circumventricular organs (CVOs). Water deprivation for 1, 2 and 3 days causes progressive increases of protein synthesis in the subfornical organ (SFO), the area postrema, the organum vasculosum laminae terminalis and the neurohypophysis. Chronic salt ingestion with 2% NaCl in drinking water for 3 days resulted in increases of protein synthesis in the CVOs similar to those found after 3 days water deprivation, with only one exception, the SFO, in which the rise in protein synthesis was of lower amplitude after 3 days salt ingestion as compared to 3 days water deprivation. These results suggest that several circulating factors related to intracellular dehydration and the high plasma levels of the neurohormones vasopressin and oxytocin are probably important determinants of the rise of protein synthesis in circumventricular organs. Alternatively, the elevated level of blood-borne angiotensin II may well explain the higher metabolic response of the SFO following water deprivation compared to salt ingestion.


Effect of arginine vasopressin on blood vessels of the perfused choroid plexus of the sheep. The perfused sheep choroid plexus was used to evaluate the response of the plexus blood vessels to systemically administered arginine vasopressin (AVP). AVP was found to decrease the diameter of the choroid plexus arterioles with a maximum change of 28 +/- 5% (mean +/- S.E.) at a plasma peptide concentration of 10(-7) M. This effect was blocked by the specific V1-vasopressinergic antagonist, d(CH2)5Tyr(Me)AVP. In contrast, venules were found not to show any appreciable response to AVP. Plasma AVP concentrations necessary to evoke a significant response of the choroid plexus arterioles are much higher than the highest plasma peptide levels observed in different physiological or pathophysiological situations. Some indirect evidence suggests, however, that AVP might be released within the choroid plexus from the vasopressinergic synaptic terminals, thus reaching a considerably high local concentration. It is possible then that the plexus vessels' tone could be controlled by the putative vasopressinergic neuronal fibers ending in the choroid plexus.


Evidence against participation of V2 receptors in the increase of cerebral blood flow during hypoxemia in the rat. Cerebral blood flow (CBF) and cerebral utilization of oxygen (CMRO2) were studied in anesthetized and artificially ventilated rats during normoxemia and hypoxemia before and during intravenous infusion of a selective blocker of V2 vasopressinergic receptors (d(CH2)5 [D-Ile2,Abu4] AVP, 15 micrograms/kg per hour i.v.). CBF was measured by means of the intracarotid 133-Xe injection method. CMRO2 was calculated from the oxygen arteriovenous difference using the Fick principle. Infusion of V2 antagonist did not influence CBF, CMRO2 or blood pressure (BP) during normoxia. It also did not change the response of cerebral circulation to hypoxemia. Increase in CBF and decrease in cerebrovascular resistance (CVR) during hypoxemia were similar during the infusion of V2 blocker or without it. However, the decrease in BP observed during hypoxemia in the control group of rats was prevented in the group of animals which were infused with V2 blocker.


ANF-induced modulation of ADH-release in the rabbit and Pekin duck. The atrial natriuretic factor (ANF) as an osmoregulatory hormone causes a reduction of extracellular fluid volume primarily through stimulation of renal and extrarenal water and sodium elimination. Consequently, ANF counteracts the renin-angio-tensin II-aldosterone (RAAS) and the antidiuretic hormone (ADH) systems at their target organ level. The possible direct interaction of ANF with the hypothalamo-neurohypophyseal ADH system was investigated in conscious ducks and rabbits during conditions of eu- and dehydration. In euhydrated animals, the plasma concentration of ADH remained unchanged during the systemic infusion of species-specific ANF, whereas in dehydrated rabbits but not ducks, the plasma concentration of ADH was significantly decreased. These differences in ADH modulation were supported by the localization of binding sites for radiolabeled ANF at the sites of ADH release, the median eminence (ME) and neurohypophysis (NH) of the rabbit but not duck brain, using receptor-autoradiography. For both species, circumventricular organs lacking a functional blood-brain barrier (BBB) such as the subfornical organ (SFO), the organum vasculosum of the laminae terminalis (OVLT), the pineal and the choroid plexus (ChP), as well as the ependymal lining of the third ventricle (VIII) were labeled specifically. Within the BBB, binding sites for ANF could not be detected in the ADH-synthesizing paraventricular (PVN) and supraoptic nuclei (SON) of either species, however, sites were observed in the anterior median nucleus of the hypothalamus (AM) of the duck brain. In the AM as well as the PVN and ME, the existence of a brain-intrinsic ANF system could be demonstrated for the Pekin duck using immunocytochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)


Neuronal plasticity depending on a glycoprotein synthesized in goldfish leptomeninx. Transcription of a calcium and zinc binding, nervous system-specific cell adhesion glycoprotein, ependymin, in goldfish leptomeninx was significantly enhanced after active avoidance conditioning, followed by enhanced translation and secretion. Inactivation of secreted ependymin by injected antisera interfered with behavioral adaptations. In addition to the site of synthesis in reticular cells of the leptomeninx electronmicroscopic immunochemistry localized the protein to tectal neurons of the superficial plexiform and the periventricular cell layers. Detection of ependymin in cells where it is not synthesized, namely in neurons, suggests a re-uptake during functional activity of the CNS and assigns a pivotal role to the cerebrospinal and interstitial brain fluids for the distribution of protein factors that support axonal growth and neuronal plasticity.


Neuropeptides within the nucleus tractus solitarii modulate the central cardiovascular control process. Local administration of small amounts of vasopressin, angiotensin or endothelin into the nucleus tractus solitarii elicits similar decreases in blood pressure and heart rate. These central effects oppose the peripheral action of these hormones on the cardiovascular system. The baroreceptor-heart-reflex, however, is influenced differentially: vasopressin and angiotensin II enhances the sensitivity of the reflex but angiotensin III impairs it. In this way the cardiovascular system may be adjusted to different demands including those related to electrolyte and fluid homeostasis.


Chromatographically identified oxytocin in the human peripheral nervous system. Immunoreactive oxytocin (OXT) detected in extracts of human coeliac ganglia and nn. vagi was characterized by high-performance liquid chromatography (HPLC). HPLC/RIA examinations demonstrated that a major part of the immunoreactive material in both investigated areas co-eluted with a reference synthetic OXT, but in the extracts of coeliac ganglia a second immunoreactive peak was also observed.


Modeling DNA structures.

Modeling DNA structures. For a molecule of biological importance, one expects a strong correlation between the three-dimensional structure and its biological function(s). Molecular simulations allow the prediction of physical properties of macromolecules. Many of these properties are closely related to the molecular structure. Model-building studies may thus supplement structurally low-resolution experimental data with detailed three-dimensional hypothetical atomic models. Such studies may give a consistent integral view of a wealth of experimental data. In most cases, such models will predict the outcome of certain experiments. Their actual results will often either confirm the model, be used for further refinement, or demand a major revision. Empirical force-fields provide a large amount of physicochemical knowledge concerning structural and other physical properties about various classes of molecules. They give reasonable bond distances and angles and prevent short van der Waals contacts. Difficulties arise for the prediction of large-scale structural elements. These are not only determined by short-range interactions, but also result from long-range electrostatic, hydration, and hydrophobic forces. In the case of the ionically driven DNA B-Z transition, the point of transition as a function of ionic strength and size can be correctly predicted (33). More must be done for a better understanding of the hydration forces (6). What type of questions will be reliably answered by a force-field? Relatively safe answers concern the local geometry of the molecules. If a conformation leads to strong distortions of bond distances or angles or to close van der Waals contacts, it can safely be rejected. Optimizing such unfavorable structures energetically may lead to structures showing how to avoid such distortions. More difficult are energetic questions: Which of two conformers is more stable, or what is the free energy of the substrate in the active site (63)? One cannot always be sure that the force-field provides the correct answers. Therefore, one should concentrate on questions that can be checked experimentally. The application of such concepts to model curved DNA (19, 60) and the DNA four-way junction (61) provides promising results. To explore the knowledge contained in the force-fields, several methods have been proposed. Taking advantage of structural symmetries may improve critically the convergence, while refining the target molecule or its building blocks. A numerically stable derivative for the torsion potential has been proposed. The optimization method of conjugated gradients (see Section II,B) is a powerful tool to find the way downhill toward a local minimum. To surmount barriers and escape local minima requires nonlocal optimization procedures.(ABSTRACT TRUNCATED AT 400 WORDS)


Development of an animal model of late asthmatic response in guinea pigs and effects of anti-asthmatic drugs. We developed an animal model of late asthmatic response (LAR) in guinea pigs and examined the effects of anti-asthmatic drugs and peptide leukotriene antagonist, MCI-826, on this model. Bronchial challenge of DNP-As (Dinitrophenylated-Ascaris suum extract)-sensitized guinea pigs induced a biphasic increase in pulmonary resistance (RL) with the maximal increase being observed immediately (IAR, immediate asthmatic response) and 3 to 5 hr after antigen inhalation (LAR). Twelve of 22 guinea pigs showed both IAR and LAR. The average increases in RL for all 22 guinea pigs at IAR and LAR, were 168 +/- 13 and 207 +/- 16 (% of baseline value), respectively. Bronchoalveolar lavage (BAL) fluid of guinea pigs that received antigen, revealed increases in the numbers of eosinophils (7.3-fold compared to animals receiving saline) and neutrophils (5.3-fold compared to animals receiving saline) 4 hr after antigen inhalation. When DSCG (disodium cromoglycate) was administered (10 mg/kg, i.v.) before antigen challenge, DSCG significantly inhibited IAR (p less than 0.05) and slightly inhibited LAR (p less than 0.2). Theophylline (30 mg/kg, p.o.) administered before antigen, slightly inhibited both IAR and LAR (p less than 0.2). Salbutamol (3 mg/kg, i.p.) administered before antigen, significantly inhibited IAR (p less than 0.05), but did not affect LAR. These results were correlated with clinical trials. Moreover, peptide leukotriene antagonist, MCI-826, (E)-2,2-Diethyl-3'-[2-[2-(4- isopropyl)thiazolyl] ethenyl]succinanilic acid (0.1 mg/kg, p.o.) administered 1 hr before antigen challenge, significantly inhibited both IAR and LAR (p less than 0.05). MCI-826 (0.1 mg/kg, p.o.) administered 1.5 hr after antigen inhalation, also inhibited LAR (p less than 0.05). Analysis of BAL fluid revealed that DSCG and MCI-826 significantly inhibited the increase in eosinophils (p less than 0.05). These data suggest that leukotriene plays an important role in the development of the pathogenesis of LAR, and that our model is an useful experimental model for investigating the mechanisms of LAR and examining the effects of several anti-asthmatic drugs on LAR.


Enhanced thromboxane formation by blood but not whole platelets from spontaneously hypertensive rats. Increased serum levels of immunoreactive thromboxane B2 (iTXB2) were observed in spontaneously hypertensive rats of the Okamoto-Aoki strain (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Serum iTXB2 levels in whole blood allowed to clot at 37 degrees C for 1 hour were significantly greater in SHR than WKY at 8, 16-20, and 38 weeks of age, whereas formation of iTXB2 by thrombin-stimulated whole platelets from 6 16-week-old SHR and 6 age-matched WKY was 399 +/- 44 and 377 +/- 38 ng/10(9) platelets/30 min, respectively. No significant difference in radioconversion of exogenous arachidonic acid to TXB2 was observed in whole platelets from SHR (18.2 +/- 2.5%, n = 4) and WKY (20.1 +/- 3.0%, n = 4) at 16 weeks of age. These results support the proposal that enhanced ability of blood from SHR to generate iTXB2 is independent of the stage of hypertension development. This enhancement probably depended on factors or blood elements other than platelets since no difference in formation was observed on stimulation of whole platelets.


PGE2 secretion from organ cultured gastric mucosa: correlation with cyclooxygenase activity and endogenous substrate release. In gastrointestinal research the in vitro release of prostaglandins from incubated or cultured biopsies is a widely used method to estimate prostaglandin synthesis. We therefore investigated the rate limiting mechanisms of PGE2 release in organ cultured gastric mucosa of the rabbit, determining PGE2 secretion from organ cultured mucosal biopsies by radioimmunoassay and prostaglandin synthesizing capacity by in vitro incubation of mucosal homogenate or microsomes with [14C]-arachidonic acid. Freshly taken biopsies secreted PGE2 at an initial high rate, that decreased during the following 4 hrs of culture. This PGE2 release was dose dependently reduced by inhibitors of the prostaglandin cyclooxygenase. 5mM acetylsalicylic acid (ASA) maximally suppressed PGE2 secretion to 7% of controls, and the inhibition by ASA was quantitatively similar at every given culture period. PGE2 release was markedly increased by carbenoxolone but was only slightly activated by extracellular calcium and the Ca(++)-ionophore A23187. However, Ca++/A23187 were unable to maintain PGE2 secretion at the initial rate. PGE2 secretion was undisturbed in calcium-free medium but was reduced to 50-60% of controls by excess EDTA. The intracellular calcium chelator 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N',-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) similarly inhibited PGE2 release to 72% of controls. In contrast, PGE2 release was unaffected by the intracellular calcium antagonist 3,4,5-trimethylene-bis(4-formylpyridinium bromide) dioxime (TMB-8), the calmodulin antagonists N-(6-aminohexyl)-1-5-chloro-1-naphthalenesulfonamide (W-7) and calmidazolium (compound R24571) or various direct inhibitors of endogenous arachidonic acid release like tetracaine, bromophenacyl bromide, neomycin or low dose quinacrine, indicating that the reduction of PGE2 release by EDTA or BAPTA may be mediated by mechanisms different from substrate release. In contrast, an inhibition of PGE2 secretion by quinacrine at high concentrations (greater than or equal to 0.8 mM) was attributed to a direct inhibition of the prostaglandin cyclooxygenase, similar to ASA. Finally, the reduction of the prostaglandin synthesizing capacity by ASA was strongly correlated with the inhibition of PGE2 secretion, also at low concentrations and minor degrees of inhibition. From these data we conclude, that the activity of the prostaglandin cyclooxygenase is rate limiting for PGE2 secretion from organ cultured mucosal biopsies rather than arachidonic acid release by a phospholipase A2. This should be considered for interpretation of studies based on prostaglandin release from cultured mucosa.


Prostanoid-induced inhibition of lipolysis in rat isolated adipocytes: probable involvement of EP3 receptors. Sulprostone, enprostil and 16, 16 dimethyl PGE2 have all been found to be potent inhibitors of lipolysis induced by 3-isobutyl-1-methyl-xanthine (IBMX) in rat isolated adipocytes. The potency of sulprostone and enprostil in particular indicates that the response is likely to be mediated through either EP3 or EP1-receptors. However, the EP1-receptor blocking drug, AH6809, had no effect on the antilipolytic response to either PGE2 or sulprostone. We therefore conclude that the receptors mediating prostanoid-induced inhibition of lipolysis in rat adipocytes must principally be of the EP3 sub-type.


Secretory diarrhea in villous adenoma of rectum: effect of treatment with somatostatin and indomethacin. The effects of treatment with the synthetic long-acting somatostatin analogue SMS-201-995 were studied in a patient with a fluid and electrolyte secreting villous adenoma of the rectum. The effects of SMS-201-995 on rectal fluid volume and electrolyte loss, and local and general prostanoid production were compared with those of treatment with indomethacin. During treatment with the somatostatin analogue iso-osmolar rectal fluid production increased about 25%; the quantity of prostaglandin E2 in the rectal fluid rose almost 20-fold. Prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha and 13,14-dihydro-15-keto-prostaglandin F2 alpha output showed similar, though less impressive increments during somatostatin treatment. The somatostatin analogue did not affect urinary prostanoid excretion except for levels of 2,3-dinor-thromboxane B2, which doubled. With indomethacin treatment diurnal rectal fluid production dropped by about 50% and all prostanoids measured in urine and rectal fluid decreased below control values. It appears that the somatostatin analogue SMS-201-995 has a marked stimulatory effect on the in vivo prostanoid production by the villous adenoma. Perhaps this stimulation is not confined to the tumor only, but also affects thromboxane synthesis.


Physiological evidence for the possible existence of anhydrolevuglandin E2-like activity in extracts and media from uteri of rats. Physiological evidence is presented for the possible existence of anhydrolevuglandin E2-like activity in extracts of uteri from diestrous rats and after treatment of adult rats with estradiol and progesterone. The extracts were able to inhibit contractions in rat uterine preparations stimulated by PGE2. Uteri of vaginal Stage 3 (metestrus) were quiescent and showed decreased responsiveness to PGE2 and PGF2 alpha. These uteri showed some contractility when incubation medium from diestrous uteri (Stage 5) were transferred to them and incubation medium from them inhibited the contractility of Stage 5 uteri. When incubation media were exchanged between contractile uteri from of stages other than Stage 3, there was no change in the contraction patterns. Taken together, we believe these data indicate that AnLGE2 may be a normal constituent of the rat uterus and is physiologically increased during Stage 3 (metestrus) of the estrous cycle.


Enhanced esterification process of 5-hydroxyeicosatetraenoic acid (5-HETE) in PMN from asthmatic patients. Polymorphonuclear neutrophils (PMN) generate 5-HETE which can be retained within cells as free metabolites or esterified into cellular lipids. Since this metabolite has been shown to have certain inflammatory properties, we compared the generation and distribution profile of 5-HETE in A 23187-stimulated PMN from asthmatic patients (AP) and normal subjects (NS). 5-HETE was analyzed using RP-HPLC. After 5 min, total 5 HETE generation was similar in the two populations. However, esterified 5-HETE was significantly enhanced in AP (72 +/- 3% versus 47 +/- 2% of the total synthesis, p less than 0.005), whereas intracellular free 5-HETE was decreased (13 +/- 3% versus 37 +/- 4%, p less than 0.005) and similar low release was observed. Kinetic studies showed that PMN from AP esterified 5-HETE more rapidly and to a greater extent than PMN from NS. By contrast, more intracellular free 5-HETE was recovered in PMN from NS. Esterification seems to be the major pathway of 5-HETE metabolism in PMN from AP. Moreover, we showed that most of the 5-HETE added exogenously was esterified into cellular lipids. In these experimental conditions, PAF-induced migration of PMN was increased. The enhanced ability of PMN to migrate could be due to the increase of 5-HETE esterification process.


Dual metabolic pathways of 12-HETE in rat aortic smooth muscle cells. 12(S)-HETE, a major lipoxygenase-derived compound from arachidonic acid is incorporated and metabolized by vascular smooth muscle cells via beta-oxidation. We have now identified for the first time in this cell type 12(S)-HETE metabolites formed by a combination of reductase and oxidation pathways. HPLC and GC-MS analysis of time-course experiments allow us to characterize two different metabolic pathways: a direct peroxisomal beta-oxidation of 12(S)-HETE leading to the formation of 16:3 (8-OH) which accumulates first and a reduction of one of the conjugated double bonds of 12(S)-HETE giving the dihydro-intermediate 20:3(12-OH) that transiently accumulates before being converted itself by peroxisomal beta-oxidation to 16:2(8-OH). Taken together these results may suggest that the transient accumulation of 20:3(12-OH) through transcellular metabolism of 12(S)-HETE may represent a part of the modulatory effect of 12(S)-HETE on vascular function.


Limited utilization of exogenous arachidonic acid by the prostaglandin cyclooxygenase in gastric mucosa: the role of protein binding, glutathione peroxidase, and hydrogen peroxides. We investigated the utilization of exogenous 14C-labelled arachidonic acid by the cyclooxygenase system of the gastric mucosa and its alteration by cytosolic factors, protein binding, glutathione peroxidase (GSH-Px), and hydrogen peroxides. Total prostaglandin (PG) synthesis from gastric microsomes was reduced in a dose- dependent manner to 12% and 68% of controls by increasing amounts of the 105,000g supernatant or albumin (8mg protein/ml), respectively (p less than 0.01). The inhibitory cytosolic factor was heat labile, protease sensitive, and was retained by a 300,000 Dalton ultrafiltration membrane. Thus, it was likely a protein. Other possible inhibitory mechanisms like protease- or heme-induced destabilization of the cyclooxygenase, haptoglobin-mediated inhibition, or self-inactivation by endogenous substrate were excluded. N-ethylmaleimide (NEM), an agent that alkylates sulfhydryl-groups thereby inhibiting GSH-Px, abolished the inhibitory effect of cytosol in a dose-dependent fashion. In contrast to their inhibition of prostaglandin synthesis, the binding of arachidonic acid by albumin or cytosolic proteins accounted to 75% and 19% under comparable conditions, respectively, however, cytosolic fatty acid binding was unaffected by NEM. Thus, it was concluded that the inhibitory effect of cytosol, in contrast to albumin, was mediated by a sulfhydryl-depending process, probably a GSH-Px. This conclusion was supported by a qualitatively comparable inhibition by a purified GSH-Px from bovine erythrocytes. The inhibitory action of cytosolic proteins was reduced significantly by increasing concentrations or repeated application of arachidonic acid; therefore, cytosolic GSH-Px was likely to affect substrate utilization by the microsomal PGH synthase through reduction of activating substrate peroxides. Similarly, the in vitro formation of cyclooxygenase products by mucosal homogenate or gastric microsomes in the absence of cytosol was limited at substrate concentrations below 80 microM, despite sufficient nonesterified arachidonic acid remaining in the incubate. This limitation was mediated only partially by self-inactivation of the prostaglandin cyclooxygenase. Neither N-ethylmaleimide nor repeated application of hydrogen peroxides increased substrate utilization by isolated microsomes, excluding contamination by GSH-Px or simply a lack of hydrogen peroxides as possible mechanisms for the limited utilization. From these results, a special role of substrate-linked lipid peroxides in the activation of mucosal prostaglandin synthesis is proposed. The reduction of these peroxides by glutathione dependent or independent peroxidases, e.g. the PGH synthase-linked hydroperoxidase activity itself, could explain the reduced utilization of nonesterified arachidonic acid by the gastric mucosa.


Relationships among mammalian gonadotropin-releasing hormone, prostaglandins, and sex steroids in the brain of the crested newt, Triturus carnifex. The present study was carried out to evaluate the in vitro brain release of prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), androgens, and 17 beta-estradiol in male and female crested newt, Triturus carnifex, during three different periods of the annual sexual cycle; in addition, the effects of mammalian gonadotropin-releasing hormone (mGnRH), PGF2 alpha, and PGE2 on prostaglandins and steroids release by the brain were evaluated during the same periods. In brain incubations of both sexes, PGF2 alpha and estradiol were higher during postreproduction, while PGE2 and androgens were higher during reproduction. In both sexes, mGnRH increased PGF2 alpha and estradiol during postreproduction, and PGE2 during reproduction; PGF2 alpha increased estradiol secretion during postreproduction. Only in the male, did both mGnRH and PGE2 increase androgens during reproduction. It could be suggested that in Triturus carnifex, the regulation of the reproductive activity in the central nervous system (CNS) depends on the relationships among mGnRH, prostaglandins and steroids. In particular, PGF2 alpha and PGE2 seem to play different roles in the CNS of the newt: PGF2 alpha is involved in the postreproductive processes, through estradiol secretion, while PGE2 in the reproductive ones (through androgens secretion?).


Platelet activation and prostacyclin release in essential hypertension. To evaluate platelet activation thromboxane A2 (TxA2) and beta-thromboglobulin (beta TG) were used as markers and in addition we studied the biosynthesis of prostacyclin. Synthesis of TxA2 and prostacyclin was assessed by measurement of urinary metabolites. Fifteen untreated hypertensive patients (HT) and 15 age-matched normotensive controls (NT) were investigated at rest, during and after exercise. HT patients were re-examined after 3 months on enalapril. During basal conditions there was no difference in the excretion of Tx-M, PGI-M or beta TG between the groups. During strenuous exercise HT exhibit a significantly higher increase in prostacyclin synthesis (162%) compared to NT (76%). The levels of beta TG increased with 82% in the HT and 24% in the NT group, Tx-M increased with 27% and 23% respectively. Treatment with the ACE-inhibitor enalapril did not significantly alter these findings. These results indicate that there is no evidence of basal platelet activation in early essential hypertension. Strenuous exercise leads to some increase in Tx-M in both groups, with no pronounced differences between the groups. Hypertensive patients exhibit a significantly increased prostacyclin response to exercise which could be due to differences in vessel-wall reactivity. Enalapril seems to exert no effect on platelet activation or on prostacyclin biosynthesis.


Proinflammatory cytokines interact synergistically with epidermal growth factor to stimulate PGE2 production in amnion-derived cells. Recent evidence has implicated cytokines and growth factors in the initiation of parturition in women. In the present study, the amnion-derived cell line WISH was used to determine whether proinflammatory cytokines (interleukins 1 beta, 6, and 8, tumor necrosis factor-alpha, and granulocyte/macrophage colony stimulating factor) could amplify epidermal growth factor-induced prostaglandin E2 production. WISH cells were preincubated with cytokines (0.0001-10 ng/ml) for 60 min and then challenged with EGF (10 ng/ml) for 4 hrs after which PGE2 production was measured by radioimmunoassay. EGF, IL-1 beta and TNF-alpha alone caused a dose-dependent increase in PGE2 production, while IL-6, IL-8 and GM-CSF were ineffective over the dose range tested. When cells were preincubated with IL-1 beta or TNF-alpha, there was a dose-dependent potentiation of EGF-induced PGE2 production that was greater than the sum of EGF alone and IL-1 beta or TNF-alpha alone. In each case, the minimum dose of IL-1 beta or TNF-alpha which amplified EGF-induced PGE2 production was 0.1 ng/ml (p less than 0.05, Student's t-test). These data show that low concentrations of IL-1 beta or TNF-alpha may serve to amplify EGF-mediated PGE2 biosynthesis in amnion-derived cells and suggest that cytokines may modulate EGF function in responsive cells.


Opioid peptides are substrates for the bifunctional enzyme LTA4 hydrolase/aminopeptidase. We determined if any naturally occurring peptides could act as substrates or inhibitors of the bifunctional, Zn2+ metalloenzyme LTA4 hydrolase/aminopeptidase (E.C.3.3.2.6). Several opioid peptides including met5-enkephalin, leu5-enkephalin, dynorphin1-6, dynorphin1-7, and dynorphin1-8 competitively inhibited the hydrolysis of L-proline-p-nitroanilide by leukotriene A4 hydrolase/aminopeptidase, consistent with an interaction at its active site. The enzyme catalyzed the N-terminal hydrolysis of tyrosine from met5-enkephalin with Km = 450 +/- 58 microM and Vmax = 4.9 +/- 0.6 nmol-hr-1-ug-1 and from leu5-enkephalin with Km = 387 +/- 90 microM and Vmax = 6.2 +/- 2.5 nmol-hr-1-ug-1. Bestatin, captopril and carnosine inhibited the hydrolysis of the enkephalins. It is noteworthy that the bifunctional catalytic traits of this enzyme include generation of an hyperalgesic substance, LTB4, and inactivation of analgesic opioid peptides.


[Dumb August. Freud's "dream interpretation" as a critique of traditional common sense]. Freud's profound scepticism about philosophy and its fondness for philosophical "systems" is well-known. From an early stage, the author of the "Interpretation of Dreams" was convinced that philosophy--like animism--was nothing other than a narcissistic attempt to explain the world systematically from one single point. That point is the ego, synthesising everything manifold, alien and threatening into an intelligible mould and subjecting it to the intellectual censorship of the cogito. Gekle shows that Freud's "Interpretation of Dreams" undercuts and decentralizes the imperialist claims of the ego, thus opening up vistas on the areas where the ego is not sole and undisputed master. At the same time, however, it becomes apparent that the decentralizing work of dream interpretation is itself confronted by a paradox. The insights gained in the process cannot be presented in any other than a theoretical, systematic and hence ego-oriented form.


[Signs of change in the affective context of dreams and the psychoanalytic process]. The author inquires whether dreams related in psychoanalysis can be indicator of curative change, and if so what affective conditions go to making this possible. To answer this question convincingly, he puts forward a new model of dream generation. It proceeds from the relation between cognitive elements, regulatory affective processes and species of interaction represented in individual dream situations. Such a model requires a new theory of mental representation, affective processes and memory. For precise analysis of change processes, Moser has recourse to a coding system for dream content. Finally he compares change processes in dreams with those in the psychoanalytic situation and suggests hypotheses on the extent to which changes in dreams can be indicators of changes in the psychoanalytic process.


[The functional correlations of dreams and transference]. The author discusses the old question about an exceptional position of the dream in psychoanalysis in a new way: he postulates the exceptional position of the dream in relation to the transference. Case material is given to illustrate how the dream report goes beyond the level of information insofar it is in itself equivalent to a specific ongoing of the transference process. In conclusion the relations between dream and transference are discussed in regard to a hypothetic functional unit.


Psychological appraisal and emotional response to physical injury: a clinical, phenomenological study of 109 adults. We studied the cognitive, emotional and behavioral responses at four points of time in a random sample of 109 accidentally injured adults via audio taped semistructured interviews and self-assessment rating scales. Neither the subjects appraisal of death or disability, nor the emotional responses corresponded strongly to the severity of the physical injury sustained or the "objective" threat to life but, instead, reflected, to a large extent, the personal meaning of the injury or the accident. Dissociative responses reported by 17 persons were of short duration and associated with young age and immaturity, and did not predict or a poor longterm post-traumatic psychiatric course. Ratings of intrusion, avoidance and anxiety were more strongly associated with psychopathology than "objective" danger or injury severity. This study indicates that following civilian trauma, the cognitive, emotional and behavioral responses are strongly related to preaccident and accident-independent life circumstances. The findings question the validity of the DSM-IIIR criterion of stressors of PTSD in civilian accidents, and suggest that post-traumatic mental disorders should be evaluated in much the same way as psychiatric disorders after physical illness.


Coping with accidental injury.

Coping with accidental injury. Coping styles and perceptual defense were studied in 20 accidentally injured adult males during hospital stay and 28 months later via clinical psychiatric and surgical examinations, the Comprehensive Psychopathological Rating Scale, Ways of Coping Checklist, Impact of Event Scale, Basic Character Inventory, the Multidimensional Health Locus of Control Scale, State Anxiety Inventory and Defense Mechanism Test. Coping styles, particularly emotion-focused coping, were more strongly correlated with underlying psychopathology than with severity of injury. Coping styles remained stable during the period of study and did not correlate with perceptual defense, state anxiety, personality traits or symptoms of post-traumatic stress. However, six specific coping efforts predicted patients who suffered from short- and long-term negative consequences with a specificity and positive predicting power of 100% and sensitivity of 69%. Results correspond to previous studies of coping with chronic illness, and suggest that somatization following physical trauma is better explained with reference to personal meaning than to a fright-model as suggested in the post-traumatic stress criteria of the DSM-III-R.


Family psychiatric history of patients with somatization disorder. We estimated the prevalence of psychiatric disability and disorders (depression, mania, schizophrenia, alcohol disorder, drug disorder, antisocial personality, and somatization) in the parents, siblings, and children of three groups of index cases: primary care patients with somatization disorder (n = 70), primary care patients who approached, but did not reach, DSM-III-R criteria for somatization disorder (n = 29), and randomly-selected community residents with no psychiatric disorder (n = 1633). Nearly all psychiatric disorders were more common in relatives of both patient samples than in relatives of community residents, and the patient samples rarely differed from each other. In the patient samples, the 22.9% rate of patients with multiple unexplained medical problems is substantially higher than previous investigations of somatization would predict. The most common disorders in patients' relatives were depression and alcohol disorder. There was little difference in the rates of depression in relatives of somatization patients who were or were not themselves depressed. A similar pattern occurred for alcohol disorder. There was a high risk for antisocial personality disorder in parents of patients meeting DSM-III-R criteria for somatization disorder, but this increase was not found for other relatives.


Psychiatric disorder and functional somatic symptoms as predictors of health care use. Data from Wave 1 of the National Institute of Mental Health Epidemiologic Catchment Area study were used to examine how functional somatic symptoms and other psychiatric disorders relate to use of health care. Panic disorder and functional somatic symptoms were strongly linked to use of general medical services while depression showed such a relationship only among females. Panic disorder and depression also showed strong association with use of mental health services, but functional somatic symptoms showed only a weak relationship. Multivariable models suggest that functional somatic symptoms lead to selective use of general medical services over mental health services.


Articulatory and phonological determinants of word length effects in span tasks. Several previous studies have shown that memory span is greater for short words than for long words. This effect is claimed to occur even when the short and long words are matched for the number of syllables and phonemes and so to provide evidence for subvocal articulation as being one mechanism that underlies memory span (Baddeley, Thomson, & Buchanan, 1975). The three experiments reported in this paper further investigate the articulatory determinants of word length effects on span tasks. Experiment 1 replicated Baddeley et al.'s finding of an effect of word length on auditory and visual span when the stimuli consist of words that differ in terms of the number of syllables. Experiments 2 and 3 showed that the effects of word length are eliminated when the words in the span task are matched for the number of syllables and phonemes but differ with respect to the duration and/or complexity of their articulatory gestures. These results indicate that it is the phonological structure of a word and not features of its actual articulation that determines the magnitude of the word length effect in span tasks.


Saccadic eye movements in Parkinson's disease: I. Delayed saccades. The saccadic eye movements of nine patients with Parkinson's disease were compared to those of nine age-matched controls in two paradigms generating volitional saccades. In both paradigms, subjects had to make delayed saccades to peripheral LED targets: a peripheral target appeared 700 msec before a buzzer sounded, the buzzer being the signal to make a saccade to the target. In the first paradigm ("centre-off"), the fixation target was extinguished simultaneously with buzzer onset. In the second ("centre-remain") it was not extinguished until 1000 msec later. The results showed that for outward saccades in both paradigms, there was no difference between Parkinsonian patients and controls, but saccadic latencies were significantly shorter in the "centre-remain" paradigm. The initial outward saccades were indistinguishable from the normal, reflex saccades of the same subjects. However, saccades returning to the centre (a type of remembered target saccade) were hypometric and showed multistepping. Both effects were more pronounced in patients with Parkinson's disease. The significance of these findings in terms of current hypotheses about the nature of the Parkinsonian saccadic deficit is discussed.


Saccadic eye movements in Parkinson's disease: II. Remembered saccades--towards a unified hypothesis? Ten patients with mild to moderate Parkinson's disease were compared with ten age-matched normal controls in a series of saccadic paradigms in order to test various hypotheses relating to the origin of the Parkinsonian saccadic defect. The paradigms comprised a reflex saccade paradigm, a standard remembered saccade paradigm, a remembered saccade paradigm with delayed centre-offset, and a remembered saccade paradigm with a second target flash immediately prior to saccade execution. Finally, subjects executed both reflex and remembered saccades in a standard remembered paradigm (the "two-saccade" paradigm). As has been reported previously, Parkinsonian subjects demonstrated hypometria on all remembered saccade paradigms, particularly the "two-saccade" paradigm. There was, however, no significant difference between the first three remembered saccade paradigms. These studies serve to refute a simple attentional capture hypothesis, and a hypothesis that suggests that the abnormality of remembered saccades is due to concurrent reflex saccade suppression. On the basis of the results, further hypotheses are advanced in an attempt to explain all published work on Parkinsonian saccades.


On the relation between time perception and the timing of motor action: evidence for a temporal oscillator controlling the timing of movement. Studies of time estimation have provided evidence that human time perception is determined by an internal clock containing a temporal oscillator and have also provided estimates of the frequency of this oscillator (Treisman, Faulkner, Naish, & Brogan, 1990; Treisman & Brogan, 1992). These estimates were based on the observation that when the intervals to be estimated are accompanied by auditory clicks that recur at certain critical rates, perturbations in time estimation occur. To test the hypothesis that the mechanisms that underlie the perception of time and those that control the timing of motor performance are similar, analogous experiments were performed on motor timing, with the object of seeing whether evidence for a clock would be obtained and if so whether its properties resemble those of the time perception clock. The prediction was made that perturbations in motor timing would be seen at the same or similar critical auditory click rates. The experiments examined choice reaction time and typing. The results support the hypothesis that a temporal oscillator paces motor performance and that this oscillator is similar to the oscillator underlying time perception. They also provide an estimate of the characteristic frequency of the oscillator.


Amnesics have a disproportionately severe memory deficit for interactive context. Two experiments were used to compare the recognition memory of amnesic and normal subjects for intentionally encoded words (targets) and for incidentally encoded words that were meaningfully related to the targets and presented at the same time (interactive context). In both experiments the target recognition of the two groups was matched at a high level by presenting the amnesics with much shorter lists of words to remember. Experiment 1 compared 20 amnesics and their matched controls and showed that whereas the amnesics' recognition of the target words did not benefit significantly when they were presented together with their interactive context words (relative to their recognition when the target words were presented alone), that of the controls did. Experiment 2 compared 14 amnesics and their matched controls and showed that when patients and their controls were matched on their target word recognition in isolation, then the patients still showed worse recognition for the interactive context words. These effects were not found only in Korsakoff patients, and their size did not correlate with behavioural measures of frontal-lobe damage. It is concluded that amnesics may be more impaired at recognizing incidentally encoded interactive context than they are at recognizing target material, and this deficit may be an essential feature of the syndrome.


A dynamical systems approach to skill acquisition. This paper argues that the answer to the question, what has to be learned, needs to be established before the question, how is it learned, can be meaningfully addressed. Based on this conviction, some of the limitations of current and past research on skill acquisition are discussed. Motivated by the dynamical systems approach, the question of "what has to be learned" was tackled by setting up a non-linear mathematical model of the task (i.e. learning to make sideways movements on a ski apparatus). On the basis of this model, the phase lag between movements of the platform of the apparatus and the actions of the subject was isolated as an ensemble variable reflecting the timing of the subject in relation to the dynamics of the apparatus. This variable was subsequently used to study "how" the task was learned in a discovery learning experiment, in which predictions stemming from the model were tested and confirmed. Overall, these findings provided support for the hypothesis, formulated by Bernstein (1967), that one of the important effects of practice is learning to make use of reactive forces, thereby reducing the need for active muscular forces. In addition, the data from a previous learning experiment on the ski apparatus--the results of which had been equivocal--were reconsidered. The use of phase lag as a dependent variable provided a resolution of those findings. On the basis of the confirmatory testing of predictions stemming from the model and the clarification of findings from a previous experiment, it is argued that the dynamical systems approach put forward here provides a powerful method for pursuing issues in skill acquisition. Suggestions are made as to how this approach can be used to systematically pursue the questions that arise as a natural outcome of the experimental evidence presented here.