Horst Köhn

Frequency of pulmonary embolism in patients who have iliofemoral deep vein thrombosis and are treated with once- or twice-daily low-molecular-weight heparin

PURPOSE The purpose of this study was to compare the efficacy and safety of treating mobile iliofemoral patients with deep venous thrombosis (DVT) with subcutaneous low-molecular-weight heparin (dalteparin sodium) either 200 IU/kg once-daily (group 1) or 100 IU/kg twice-daily (group 2). METHODS Consecutive patients with suspected iliofemoral DVT diagnosed by duplex ultrasonography and verified by radionuclide venography were randomized to one of the two low-molecular-weight heparin (LMWH) regimens. Perfusion and when necessary ventilation scans were performed for diagnosis of pulmonary emboli (PE) in all patients immediately after admission and were repeated after approximately 10 days, whereupon oral anticoagulation was started unless contraindicated. Minimal and maximal anti-factor Xa activity was measured after 2 to 3 days of therapy. All patients were kept mobile with compression bandages. The primary end point was reduction in frequency of PE as assessed on the second lung scan. RESULTS A total of 140 patients with confirmed DVT were randomized, 76 to group 1 and 64 to group 2. The two groups were comparable in their baseline clinical characteristics. In the initial lung scans 36 (47.4%) patients in group 1 and 29 (45.3%) patients in group 2 had objectively verified PE, but only 11 (14.5%) and 8 (12.5%) patients, respectively, had symptoms. After dalteparin treatment PE disappeared in two patients in group 1, but in two other cases new PEs occurred, (NS). In group 2 a resolution of PEs was observed in eight patients, whereas only one new PE could be detected. This change reflects the efficacy of therapy as defined by resolution of existing PEs and by the occurrence of new PEs and is statistically significant according to McNemars chi-square test with the exact binomial method pair procedure (p < 0.05). Symptomatic PE was reduced from 14.5% to 5.3% in group 1 (96% to CI for the difference, -1.5% to +17.3%) and from 12.5% to 1.6% in group 2 (95% CI for the difference 0.7% to 18%, p < 0.05). There was one single fatal PE, one serious and three minor bleeding episodes in group 1, and one minor bleeding episode in group 2 (95% CI for the difference: -3.6% to +8.1%). CONCLUSIONS Treatment of ambulant iliofemoral patients with DVT with 100 IU/kg dalteparin twice-daily appears to be moe safe and effective than 200 IU/kg given once-daily. Bed rest is not necessary for treating mobile patients.

Frequency of pulmonary embolism in ambulant patients with pelvic vein thrombosis: A prospective study

One hundred thirty-nine consecutive patients (average age 70.1 years) who were able to walk with a swollen leg were seen at the clinic where diagnosis of acute deep vein thrombosis (DVT) extending to the pelvis was confirmed by injecting microspheres labeled with technetium 99m into the dorsal foot vein (radionuclide venography). Thirty-nine (28%) of these patients had malignant disease. Perfusion lung scans performed immediately after radionuclide venography were supplemented by inhalation scans (99mTc-labeled diethylenetriamine pentaacetic acid aerosol) in case of perfusion defects. During scintigraphy patterns highly indicative of pulmonary embolism (PE) were found in 80 patients (58%), but only 11 (7.9%) had minor clinical symptoms. All patients were admitted to the ward, were given standard heparin subcutaneously (35,000 to 40,000 units/24 hr) and firm bandages, and were encouraged to walk. After 11 days pulmonary scintigraphy was repeated and revealed no change in 55 of 59 patients without PE and in 40 of 80 patients with PE. Thirty-three patients (23.7%) showed regression of perfusion defects. New PE developed in 11 patients (7.9%, four without and seven with previous PE). Autopsy revealed that one 80-year-old patient with prostatic carcinoma had died of massive PE. When comparing this frequency of newly developed PE during ambulation with the occurrence of PE after bed rest, according to the literature, it is no more dangerous for a mobile patient with proximal DVT to walk wearing a firm bandage than it is for the patient to be in bed. Therefore we recommend treating mobile patients with DVT by use of anticoagulation and firm compression bandages and without immobilization.

67Ga scanning for assessment of disease activity and therapy decisions in pulmonary sarcoidosis in comparison to chest radiography, serum ACE and blood T-lymphocytes.

In 60 patients with histologically proven sarcoidosis, 67Ga scanning was evaluated in terms of sensitivity and specificity for assessing disease activity and compared with chest radiography, serum ACE and blood T-lymphocytes. While 67Ga scans had the highest sensitivity (94%), the specificity was only 68%. The sensitivity of chest radiography was 80%, of serum ACE and blood T-lymphocytes 77% and 48%, respectively. While in patients with radiographical type I, 67Ga scanning, chest radiography and serum ACE had a sensitivity of 92%–100%, in patients with radiographical type II–III, only 67Ga scans had a sensitivity exceeding 90%. A 67Ga score correlated significantly with serum ACE levels (r=0.59, P<0.001).After effective steroid treatment, 67Ga uptake and serum ACE activities decreased markedly. While in 25% of cases, chest radiography failed to provide reliable information, 67Ga scanning and serum ACE activities always proved useful in evaluating the course of the disease and the patients response to steroid therapy. A negative 67Ga scan together with normal serum ACE levels seen to have a high predictive value for excluding active sarcoidosis.

Alveolar macrophages of patients with adult respiratory distress syndrome express high levels of heat shock protein 72 mRNA.

Adult respiratory distress syndrome (ARDS), a multifactorial disease with poor prognosis, is characterized by an accumulation of inflammatory cells within the airspaces of the lungs. There is evidence that alveolar macrophages (AM) are involved in the pathogenesis of this pulmonary disease. It has been demonstrated that AM synthesize heat shock proteins (HSPs) after exposure to certain stress factors. Increasing evidence suggests that HSPs could confer protection against oxidative injury, noxious molecules, and bacterial toxins. In stressed cells HSP 72 appears to be essential for survival during and after exposure to cellular injury. The aim of this study was to evaluate the magnitude of HSP 72 expression by human AM of patients with ARDS and correlate that with respiratory burst activity. Bronchoalveolar lavage was performed in six ARDS patients, 10 patients with high risk for developing ARDS, and two patients who underwent bronchoscopy for other reasons. Spontaneous ex vivo expression of HSP 72 in AM could be demonstrated by immunocytochemistry. Total RNA as well as poly(A)-rich mRNA were extracted from recovered AM and analyzed by Northern blot and slot blot using a human HSP 72-specific probe. Signals of slot blot were analyzed by densitometry and expressed as relative levels of HSP 72 mRNA of stressed (42°C) HT 1080 control cells. Significantly (p < .001) higher levels of HSP 72 mRNA were measured in patients with ARDS (96.2 ± 9.5 relative levels) in comparison to those not developing this syndrome (46.0 ± 4.2). With regard to respiratory burst activity of AM in patients with ARDS, there was a negative correlation between HSP 72 expression and reactive oxygen species production. The AM of patients with ARDS with high relative levels of HSP 72 expression showed low respiratory burst activity. A predictive value for disease severity of high level of HSP 72 mRNA in AM in patients at risk for ARDS has to be evaluated by future studies. This demonstration of HSP 72 expression ex vivo suggests a protective role of HSP response against endo/exogenously generated stress factors in AM.

Incidence and clinical feature of pulmonary embolism in patients with deep vein thrombosis: A prospective study

In 169 patients with suspected deep vein thrombosis (DVT), the incidence and clinical feature of pulmonary embolism (PE) was prospectively studied by means of noninvasive thrombosis tests (uptake tests, radionuclide venography) and combined ventilation (133Xe, 81mKr) and perfusion (99mTc microspheres) lung scanning. DVT was detected in 62% of patients (105/169). The incidence of PE in patients with confirmed DVT was 57% (60/105), a figure which is in excellent agreement with data from autopsy studies. Concerning the thrombotic source of emboli, the incidence of PE was 46% in patients with DVT confined to the calf but increased to 67% if the thigh, and to 77% if the pelvic veins were involved as well. Fifty-nine percent of PE were clinically silent, 19% had “minor signs”, and 22% “major signs”. The size of the perfusion defects correlated significantly with clinical symptoms. Only 23% of clinically sumptomatic patients had a pathological chest X-ray. Incidence of both DVT and PE increased with advancing age, but in old patients the incidence of PE rose disproportionately.

99mTc-DTPA aerosol for same-day post-perfusion ventilation imaging: Results of a multicentre study

A multicentre study was performed in an attempt to evaluate a submicronic technetium-99m diethylene triamine penta-acetic acid aerosol generated by a newly developed delivery system, the aerosol production equipment (APE nebulizer), for same-day post-perfusion ventilation imaging in patients with clinically suspected pulmonary embolism. Quantitative comparison between the DTPA aerosol and krypton gas demonstrated a close correlation with respect to regional pulmonary distribution of activity and peripheral lung penetration (n=14,r=0.94,P<0.001 andr=0.75,P<0.0025, respectively). In 169 consecutive patients, DTPA aerosol images performed immediately following perfusion (inhalation scan I) were compared to those carried out on the next day (inhalation scan 11) with respect to image quality and assessment of perfusion-ventilation matches or mismatches. Agreement between inhalation scans I and II with respect to perfusion defects matched or mismatched to ventilation was found in 166/169 (98%) studies. The image quality of inhalation scan I was equal to that of scan II in 72%; inhalation scan I was superior in 11% of cases, while scan 11 was superior in 17%. This submicronic99mTc-labelled DTPA aerosol is well suited for fast same-day post-perfusion ventilation imaging in patients with clinical suspicion of pulmonary embolism.

Dry aerosol of monodisperse millimicrospheres for ventilation imaging: production, delivery system, and clinical results in comparison with 81m-krypton and 127-xenon.

The production of monodisperse human albumin millimicrospheres (diameter <1 μm) and labeling with 99mTc is described. A system constructed to nebulize and deliver a dry aerosol yielded a lung delivery efficiency of approximately 25%. In 48 patients without and with varying degrees of chronic obstructive lung disease, quantitative comparison with 81mKr (penetration index, regional distribution of activity in the lungs) demonstrated similar penetration of the particles to the lung periphery (r=0.89 and r=0.94, respectively). Qualitative comparison with 81mKr or 127Xe showed complete or a high degree of diagnostic agreement in all but one patient. Semiquantitative scoring of hot spots as a substrate of local turbulent airflow showed a close inverse correlation (r=-0.82) with the forced expiratory volume in 1 s (FEV 1.0%), thus providing additional information about the severity of the airway obstruction. In 24 patients with suspected pulmonary embolism, complete agreement between aerosol and 81mKr images was found in all patients studied. For same-day ventilation/perfusion studies, labeling of the millimicrospheres with 111In yielded images of comparable quality to those obtained with the 99mTc-labeled aerosol.

Value of additional lateral scans in renal scintigraphy

Although it is common to perform scintigrams in multiple projections this technique has not yet been generally accepted for kidney scintigraphy.By performing additional lateral scans using an Anger camera and with patients sitting we found at least three advantages:1.Better Visualisation of Kidney Lesions: 7 (13,5%) of 52 cases with lesions could be detected in lateral projection only, in all other cases we obtained better information concerning location and size of lesions.2.Determination of Real Kidney Size: Of 62 patients with kidneys appearing reduced unilaterally in the dorsal projection, additional lateral recordings demonstrated that 24 (39%) seemed diminished because of tilting.3.Better Interpretation of Renograms: Demonstration of different depths of kidneys facilitates interpretation of renograms with different peak heights. Additional lateral scans thus can provide — at least if dorsal recordings are inconclusive — further information.

Immunoreactive trypsin, α-amylase and lipase in serum — Is there an age-dependence?

A strong age-dependence of IR trypsin was found in 424 healthy controls suggesting the need for age-matched reference values. A possible relation of other exocrine pancreatic enzymes like alpha-amylase and lipase to age was investigated in 185 apparently healthy persons undergoing a preventive health check. Only alpha-amylase showed a weak correlation with age, but not lipase. Both enzymes correlated with IR trypsin. Whilst alpha-amylase and lipase activities were within the normal range, approximately 25% of IR-trypsin concentrations were above age-matched control values. It is suggested that these apparently healthy persons already have disease of the exocrine pancreas, and IR trypsin is a more sensitive diagnostic tool for screening than alpha-amylase or lipase.

Non-Invasive Screening for Deep Vein Thrombosis: Comparison between 99mTc-labelled Compounds, Thermography, 131 I-Fibrinogen Uptake Test and X-Ray Phlebography

In 81 patients with clinically suspected deep vein thrombosis, the diagnostic accuracy of thermography, 99m Tc-plasmin and 99m Tc-fibrinogen uptake tests for detecting and localizing DVT was compared with a routinely used 131 I-FUT and X-ray phlebography as reference method. Sensitivity of these tests for detection of DVT was high (0.86–1.0). 99m Tc-labelled compounds and thermography should be used for detecting rather than for localizing DVT, since sensitivity of these tests was somewhat lower in the thigh. Clinical examination and exclusion of patients with inflammatory processes, hematoma or trauma markedly increases the specificity. Uptake tests with 99m Tc-labelled compounds are fast, reliable and suitable as bedside tests.