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Biomedical subjects

P Vock

Publications and source records attributed to P Vock.

At least 55 records · Page 3Linked to original sources

2-Aminobenzoyl-CoA monooxygenase/reductase. Evidence for two distinct loci catalyzing substrate monooxygenation and hydrogenation.

2-Aminobenzoyl-CoA monooxygenase/reductase catalyzes both monooxygenation and hydrogenation of anthraniloyl-CoA. Its reactivity with 11 substrate analogs has been investigated. Only 2-aminobenzoyl-CoA (anthraniloyl-CoA) in its normal and deuterated (5-2H) form is a full substrate, and only traces of 2-hydroxybenzoyl-CoA (salicyloyl-CoA) are probably monooxygenated but not hydrogenated. The purified enzyme is a homodimer and has been resolved preparatively into three major species by anion-exchange chromatography on Mono Q. All three species have the same specific activity when reconstituted to full content of FAD, they differ, however, substantially in their mode of binding FAD. The oxidized or fully reduced enzyme forms bind tightly 0.5 mol/mol of the substrate 2-aminobenzoyl-CoA (Kd = 1-2 microM). The enzyme can be depleted of approximately 50% of its FAD, which corresponds to essentially complete removal from one of the two binding sites, reflecting a large difference in the affinity for FAD. From this it is deduced that the two sites are not equivalent. Removal of FAD from one binding site leads to loss of the hydrogenation capacity of the enzyme, while monooxygenation catalysis is retained. The FAD cofactors of the two binding sites differ drastically in their reactivities towards NADH, oxygen and N-ethylmaleimide. Exchange of reducing equivalents between the two FAD cofactors at the respective binding sites is very slow and irrelevant compared to the rates of catalysis. It is concluded that the enzyme, which has been proposed to consist of two identical polypeptide chains [Altenschmidt, U., Bokranz, M. & Fuchs, G. (1992) Eur. J. Biochem. 207, 715-722], contains two active centers which differ substantially in their catalytic activity. One center belongs to the class of monooxygenases, the other one to the (de)hydrogenases. This must result from substantially different interaction of the same flavin cofactors with protein functional groups and is, to our knowledge, unprecedented in flavoprotein enzymology.

Catalysis↗

[Aortic elongation: merely mimicked in increased thoracic kyphosis? radiologic-pathologic correlation].

The purpose of this investigation was to demonstrate that the radiologically "elongated" thoracic aorta corresponds to an increase in anatomical aortic length and is not merely mimicked by increased thoracic kyphosis with shortening of the thoracic cage. 50 consecutive autopsies were included (age at death: 33-90 years, mean 65.1 years). Radiologically, mediastinal width was measured on in vivo posteroanterior radiographs, and a scoring system was used to assess aortic elongation semiquantitatively. The angle of kyphosis was measured on lateral in vivo radiographs that had been obtained in a standardized fashion. With relative aortic length defined as anatomical aortic length divided by body length, there was a statistically significant correlation with radiological mediastinal width and the radiological scoring system (p < 0.001). However, there was no statistically significant correlation between relative aortic length and radiological mediastinal width (p = 0.47) and the radiological scoring system (p = 0.56). Therefore, the radiological diagnosis of aortic elongation appears to correspond to true aortic lengthening.

Adult↗

Neoplastic invasion of the laryngeal cartilage: comparison of MR imaging and CT with histopathologic correlation.

PURPOSE: To compare the usefulness of computed tomography (CT) and gadolinium-enhanced magnetic resonance (MR) imaging in the detection of neoplastic invasion of laryngeal cartilage. MATERIALS AND METHODS: In a prospective study, 53 patients with carcinoma of the larynx or piriform sinus underwent CT and MR imaging before total or partial laryngectomy. The findings at imaging and pathologic examination were compared. RESULTS: At histologic examination, neoplastic invasion of cartilage was present in 34 patients and absent in 19. MR imaging was more sensitive than CT (89% vs 66%; P = .001). Inflammatory changes and fibrosis, however, were indistinguishable from tumor on MR images, resulting in overestimation of neoplastic invasion in a large number of patients. Therefore, MR imaging was less specific than CT (84% vs 94%; P = .004). CONCLUSION: MR imaging is more sensitive than CT in detecting neoplastic invasion of cartilage, but the inability to differentiate between nonneoplastic inflammatory changes and tumor with MR imaging leads to overestimation of neoplastic invasion.

Carcinoma, Squamous Cell↗

Radiation exposure of patients who undergo CT of the trunk.

PURPOSE: To determine the radiation dose delivered to organs during standard computed tomographic (CT) examination of the trunk. MATERIALS AND METHODS: In vivo locations and sizes of specific body organs were determined from CT images of patients who underwent examinations. The corresponding CT investigations were then simulated on an anthropomorphic phantom. The resulting doses were measured at 70 different sites inside the phantom by using thermoluminescent dosimeters. On the basis of measurements of free-in-air air kerma at the rotation axis of the CT gantry, conversion factors were calculated so that measurements could be used with different models of CT equipment. RESULTS: Starting from the dose values recorded, the mean organ doses were determined for 21 organs. The skin received 22-36 mGy; the lungs, less than 1-18 mGy; the kidneys, 7-24 mGy; and the ovaries, less than 1-19 mGy, depending on the type of CT examination performed. CONCLUSION: These values are high compared with other x-ray examinations and should be minimized as much as possible. The number of tomographic sections obtained should be kept as low as possible according to diagnostic need.

Adult↗

Nifedipine does not prevent acute mountain sickness.

Nifedipine has been shown effective for prevention and treatment of high altitude pulmonary edema (HAPE). Because acute mountain sickness (AMS) and HAPE may share common pathophysiologic mechanisms, we evaluate the prophylactic effect of nifedipine on the development of AMS in 27 mountaineers not susceptible to HAPE. They were randomly assigned to receive in a double-blind manner either nifedipine or placebo during rapid ascent to 4559 m and a subsequent three-day sojourn at this altitude. Nine of 14 subjects on nifedipine and eight of 13 subjects on placebo felt ill at high altitude. Pulmonary artery pressures (PAP) estimated by Doppler echocardiography were significantly lower with nifedipine, but arterial PO2, oxygen saturation, and alveolar-arterial oxygen pressure gradient were not significantly different between groups at high altitude. This study demonstrates that lowering PAP has no beneficial effect on gas exchange and symptoms of AMS in subjects not susceptible to HAPE. Therefore, nifedipine cannot be recommended for prevention of AMS, and its use in high altitude medicine should be limited to prevention and treatment of HAPE.

Acute Disease↗

[Radiological diagnosis of lung tumors].

Tumor detection, differential diagnosis, clinical staging and follow-up information are the main aims in imaging lung tumors. The contribution of specific imaging methods, above all chest radiography and CT, is discussed for lung cancer, the clinically most important entity. Despite the lack of histologic information, noninvasive methods currently play an important role in the clinical management of lung tumors.

Carcinoma, Non-Small-Cell Lung↗

[The accuracy of intravenous digital subtraction angiography regarding kidney arteries in hypertensive patients. A contribution to cost control in diagnostic medicine].

In a retrospective study the results of intravenous digital subtraction angiography (DSA) of renal arteries from 149 hypertensive outpatients investigated 1984 to 1989 at the University of Berne were evaluated. 118 i.v. DSA's (79%) were normal, 10 (7%) were inconclusive and 21 (14%) revealed stenosis. In 16 patients the course of the vessel and the degree of stenosis were verified by intraarterial DSA. In nine patients (6%) a significant stenosis was confirmed and subsequently treated by percutaneous transluminal angioplasty. Renal size was not a predictive parameter for stenosis in this population. Accessory renal arteries were found in 44% of patients with stenosis and only in 18% of those without. The late phase images of i.v. DSA revealed many morphologic abnormalities. The indication for i.v. DSA was assessed according to internationally accepted criteria: 1. severe hypertension, 2. hypertension refractory to treatment, 3. hypertension of sudden onset or aggravation, 4. onset of hypertension in patients younger than 20 or older than 50 years. In the group without stenosis (n = 118) 52 patients (44%) did not fulfill a single one of these criteria, whereas the patients with stenosis (n = 9) had at least one criterion fulfilled. Hypertensive patients should, therefore, only be studied by i.v. DSA if at least one criterion applies. 22,000 SFr. could thus have been saved without loss of medical quality and the treatment options.

Angiography, Digital Subtraction↗

[Internal bleeding in patients on oral anticoagulants].

Five selected case reports of patients suffering from rather unusual bleeding complications during oral anticoagulant therapy are presented. The reported frequency of bleeding during oral anticoagulation varies greatly. An unacceptably high incidence of hemorrhages has been reported in North American studies of the early 1980ies. The therapeutic target INR of 2.5-4.9 in these series is comparable to that in European studies where bleeding occurred much less frequently. We suggest that the insensitive thromboplastin reagents used in North America are unsuited to guide coumarin dosage, because too many prothrombin time values were outside the INR target range. In contrast, most prothrombin time values in European studies where a sensitive thromboplastin reagent was used, were within the target range. A recent prospective investigation by 25 Swiss practitioners showed an acceptably low bleeding complication rate (2.1 hemorrhagic complications severe enough to necessitate hospitalization per 100 patient years). Observation of contraindications, regular control of the prothrombin time using a sensitive and correctly calibrated thromboplastin, participation of practitioners and hospital laboratories at quality control exercises and consideration of drug interferences with coumarins help to reduce the incidence of hemorrhagic side effects. In case of either a PT value outside the target range or manifest bleeding, the necessary measures have to be tailored to the individual situation considering the Quick value as well as the severity and localization of hemorrhage.

Abdominal Muscles↗

[Morphological changes of the lower leg arteries and the plantar arch in diabetic and nondiabetic patients with chronic critical ischemia of the leg].

In this prospective study we evaluated if atherosclerosis of crural and pedal arteries differs in diabetic and non-diabetic patients suffering from chronic ischemia. We performed intraoperative angiography after completion of a femoro-popliteal or femoro-distal bypass. No statistically significant difference was found between the two groups (25 diabetic and 44 non-diabetic patients) concerning the severity and localisation of the arteriosclerosis in the three crural arteries and the pedal arch. The prerequisite for a successful arterial reconstruction were identical in our patients with or without diabetes and a similar number of potential recipient arteries were found at below knee and foot level in both groups.

Aged↗

Spiral computed tomography in the assessment of focal and diffuse lung disease.

Conventional computed tomography (CT) processes the raw data of a single rotation at any given level to produce the image at that level. Scan collimation and interspacing are determined prospectively. Spiral CT combines longitudinal patient transport with continuous data acquisition. Interpolated projections are used for reconstructing any level inside the scanned volume. Therefore, spiral CT allows any number of images, their spacing, position, and field of view to be determined retrospectively. Technically, the only limiting factors of spiral CT are the load of the x-ray tube and the computation power of the scanner. Spiral CT is superior to conventional CT in detecting lung nodules, in imaging the representative slice of a small nodule by retrospective selection, and in its ability to reformat the image in any plane. It also allows rapid scanning and three-dimensional re-formation of images. It may reduce the dose of contrast agent required for optimal enhancement of the vascular structures, reduce the radiation dose, and eliminate motion artifacts.

Adult↗

Vertical LM sectioning and parallel CT scanning designs for stereology: application to human lung.

Practical, unbiased stereological methods are described to estimate lung volume and external surface area, and total volume and surface area of relatively large and anisotropic structures (bronchi and arteries) inside the lung. The volume of each of five lung strata was estimated first by fluid displacement and then by computed tomography (CT) using Cavalieri's method; the reliability of CT was assessed through a calibration procedure, and image thresholding criteria for an accurate volume estimation using CT were established. The parallel, perfectly registered CT section images were also used to estimate the external surface area of each stratum by the spatial grid method. Unbiased estimation of internal surface areas in lung is a long-standing problem: since the structures are large and essentially void, large sections are needed; to facilitate identification, thin sections have to be used for light microscopy, and since such structures are anisotropic, the sections should be vertical. A practical stereological design is demonstrated here on an infant lung, which fulfils all these requirements. This study illustrates the potential of using unbiased stereology to characterize infant pulmonary hypoplasia.

Female↗

[Dental caries (DMFT) in adults in Switzerland 1988].

In 1988, 864 adults were examined for dental and periodontal conditions in 47 dental offices in Switzerland according to WHO methods. Among the 57 offices selected at random 10 dentists were unwilling to cooperate. Within each office, 36 patients were chosen by a randomizing mechanism. 51 percent of the selected patients presented themselves for the examination whereas 14 percent refused to participate in the study; of the remaining subjects one third could not be reached during the three to five days available for contacting them and two thirds were unable to come to the respective dental office at the preset day of examination. The DMF data obtained were similar to the results of previous local surveys, part of which were based on random samples. Up to age 74, it was concluded that the data of the present survey are fairly representative of the Swiss resident population. In the age group 75 and above, the number of missing teeth (MT) was too low, mainly due to edentulous persons, institutionalized and other, being obviously underrepresented. The Swiss DMFT of 22.3 in the age group 35-44 was almost the highest mean among 26 European countries. However, prevention efforts at school age, already obvious in the age group 30-34, will substantially improve the results at age 35-44 by the year 1998. The number of DT was 1.0 and 1.3 for the ages up to 29 and below 1.0 in the older groups. Up to age 54, FT was the most important component of the DMFT while in the older groups, MT was highest.

Adult↗

[MR angiography of the abdomen].

The two techniques currently most often used for MR angiography, those based on time-of-flight effects and on phase-contrast, are introduced, and our results with three-dimensional phase contrast angiography of the abdomen are presented. Several basic differences from other imaging procedures render MR angiography clinically useful for screening for renal artery stenosis in critical situations, such as renal failure or intolerance to contrast agents. In the future, the spectrum of applications of MR angiography will broaden and include other indications, such as portal venous hypertension and follow-up studies after surgical portal systemic shunting.

Abdomen↗

[Pathophysiology, prevention and therapy of altitude pulmonary edema].

Alveolar hypoxia and resulting tissue hypoxia initiates the pathophysiological sequence of high altitude pulmonary edema (HAPE). Very rapid ascent to high altitude without prior acclimatization results in HAPE, even in subjects with excellent tolerance to high altitude. Upon acute altitude exposure, HAPE-susceptible individuals react with increased secretion of norepinephrine, epinephrine, renin, angiotensin, aldosterone and atrial natriuretic peptide. In response to exercise at high altitude, subjects developing acute mountain sickness and HAPE secrete more aldosterone and antidiuretic hormone than subjects who remain well. This results in sodium and water retention, reduction of urine output, increase in body weight and development of peripheral edemas. The hypoxic pulmonary vascular response is enhanced in HAPE-susceptible subjects, thus favouring the development of severe pulmonary hypertension on exposure to high altitude. It has been postulated that uneven pulmonary vasoconstriction enhances filtration pressure in non-vasoconstricted lung areas, leading to interstitial and alveolar edema. The high protein content of the edema fluid in HAPE characterizes this edema as a permeability edema. The prophylactic administration of nifedipine prevents the exaggerated pulmonary hypertension of HAPE-susceptible subjects upon rapid ascent to 4559 m and thus prevents HAPE in most cases. This finding illustrates the crucial role of hypoxic pulmonary hypertension in the development of HAPE. The causal treatment of HAPE is descent, evacuation and administration of oxygen. Treatment of HAPE patients with nifedipine results in a reduction of pulmonary artery pressure, clinical improvement, increased oxygenation, decrease of the alveolar arterial oxygen gradient and progressive clearing of pulmonary edema on chest x-ray. Thus nifedipine offers a pharmacological tool for the treatment of HAPE.

Aldosterone↗

Alterations in hepatic fructose metabolism in cirrhotic patients demonstrated by dynamic 31phosphorus spectroscopy.

Quantitative liver function tests are based on the clearance concept and measure the plasma disappearance of a test compound such as galactose. Metabolism is inferred to be predominantly hepatic, and usually no knowledge is obtained of the true time course of metabolite formation. Dynamic 31phosphorus magnetic resonance spectroscopy after intravenous administration of fructose directly measures hepatic sugar metabolism. To determine the feasibility and the utility of 31P magnetic resonance spectroscopy, we studied the responses of six healthy subjects and nine patients with nonalcoholic cirrhosis to a fructose load. Results were related to the impairment of hepatic function assessed by the galactose-elimination capacity test. Liver spectra were acquired in a 1.5 T whole-body nuclear magnetic resonance unit with a surface coil (9-cm diameter) placed ventrally on the liver; the one-dimensional chemical-shift imaging technique was used to obtain spectra from tissue slices parallel to the surface coil. After a basal spectrum had been obtained, fructose (250 mg/kg) was injected intravenously, and further spectra were collected sequentially every 6 min for 1 hr. Formation of monophosphate esters (9% +/- 5% vs. 20% +/- 8% of total area; p less than 0.01) and utilization of inorganic phosphate (5% +/- 4% vs. 11% +/- 3% of total area; p less than 0.005) were markedly decreased in cirrhotic patients. These measures correlated with the severity of the impairment of liver function measured by the galactose-elimination capacity (r = 0.53 to 0.69; p less than 0.05). We conclude that dynamic 31P magnetic resonance spectroscopy is a safe, clinically feasible test that allows detailed insights into biochemical events in liver disease.

Adenosine Triphosphate↗

Prevention and treatment of high altitude pulmonary edema by a calcium channel blocker.

High altitude pulmonary edema (HAPE) is characterized by marked pulmonary hypertension. Treatment of 6 subjects suffering from radiographically documented HAPE with the calcium channel blocker nifedipine, lowered pulmonary artery pressure and resulted in clinical improvement, better oxygenation, reduction of alveolar-arterial oxygen gradient and a progressive clearing of alveolar edema on chest x-ray. This amelioration occurred despite continued exercise at an altitude above 4000 m and without supplementary oxygen. Prophylactic application of nifedipine slow release preparation, 20 mg every 8 hours, prevented HAPE in 9 out of 10 subjects with a history of radiographically documented HAPE upon rapid ascent and subsequent stay to an altitude of 4559 m. Seven of 11 comparable subjects who received placebo developed pulmonary edema at 4559 m. As compared with the subjects who received placebo, those who received nifedipine had a significantly lower mean systolic pulmonary artery pressure, alveolar-arterial pressure gradient of oxygen and symptom score of acute mountain sickness at 4559 m. Thus nifedipine offers a potential emergency treatment of HAPE when descent or evacuation is impossible and oxygen is not available. Prophylactic administration of nifedipine prevents HAPE in susceptible subjects. High pulmonary artery pressure has an important role in the pathogenesis of HAPE.

Acute Disease↗

Effect of reduced expiratory pressure on pharyngeal size during nasal positive airway pressure in patients with sleep apnoea: evaluation by continuous computed tomography.

BACKGROUND: This study aimed to determine whether reducing the expiratory pressure during nasal positive airway pressure for reasons of comfort causes a substantial decrease in the upper airway calibre. METHODS: Eight patients with obstructive sleep apnoea were studied. Continuous computed tomography (each run lasting 12 seconds) was used to measure minimum and maximum pharyngeal cross sectional areas at the velopharynx and the hypopharynx. Pharyngeal areas were measured while patients were awake and breathing without assistance, during the application of 12 cm H2O continuous positive airway pressure, and during bi-level positive airway pressure with an inspiratory pressure of 12 cm H2O and an expiratory pressure of 6 cm H2O. RESULTS: Nasal continuous positive airway pressure significantly increased the mean minimum and maximum upper airway areas at both the velopharynx and the hypopharynx compared with normal unassisted breathing. Bi-level positive airway pressure did not show a statistically significant increase in the minimum upper airway area at either level compared with normal unassisted breathing. The minimum areas of the velopharynx and hypopharynx were smaller with bi-level than continuous positive airways pressure in six of eight and eight of eight patients respectively but these were still greater than during unassisted breathing in seven of eight and six of eight patients respectively. CONCLUSIONS: Continuous positive airway pressure at 12 cm H2O is more effective in splinting the pharynx open than bi-level positive airway pressure with an inspiratory positive airway pressure of 12 cm H2O and an expiratory pressure of 6 cm H2O in patients with obstructive sleep apnoea during wakefulness, suggesting an important role for expiratory positive airway pressure. The clinical importance of this finding needs to be evaluated during sleep.

Humans↗

[Radiologic and nuclear medicine diagnosis of lung embolism].

The imaging methods used in diagnosing pulmonary embolism and their appropriate indication in individual situations are discussed. Chest radiography is needed to exclude other diseases, whereas nuclear ventilation and perfusion scans are the main screening method and have not been replaced by intravenous digital subtraction angiography up to now. As long as these non-invasive methods are clearly negative or positive, no other method is needed. With questionable findings (intermediate scan probability), pulmonary angiography is needed, above all when there is a contraindication to anticoagulation.

Angiography, Digital Subtraction↗