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CD14 as marker for liver allograft rejection?
60
the presence of a thin layer of fibrin, some thrombus formation is essential for healing.3.4 The key reaction in the blood coagulation system cascade is the conversion of prothrombin to thrombin. During this process, factor Xa cleaves prothrombin, which results in the generation of both PTF and thrombin. In the presence of heparin, the serine protease can rapidly be neutralised by antithrombin III, which forms an inactive thrombin-antithrombin III complex (TAT). Both PTF and TAT can be regarded as molecular markers of a prethrombotic state .2 PTF is a useful marker that indicates an evolving subacute occlusion of the stented segment if concentrations are over 0-5 nmol/1. Dose reduction of heparin-even at therapeutic prothrombin time ratios-should therefore be avoided if PTF exceeds 0-5 nmol/1. HOLGER SWARS GERD HAFNER RAIMUND ERBEL WOLFRAM EHRENTHAL II Medical Clinic, HANS JÜRGEN RUPPRECHT and Institute of Clinical Chemistry, WINFRIED PRELLWITZ Johannes Gutenberg University, D 6500 Mainz 1, Germany JURGEN MEYER
of alcohol causes an accumulation of acetaldehyde and brings on nausea and vomiting. However, these drugs have disadvantages; the optimum dose and dosage schedule is not established, and they have adverse reactions and several contraindications with deleterious drug interactions.’ Zimeldine, which blocks serotonin uptake, decreased the daily intake of alcohol and increased the percentage of days of abstinence in chronic alcoholics.3However, the drug was withdrawn world wide because of reports of hepatitis and Guillain Barre syndrome. From these preliminary fmdings we conclude that ritanserin effectively decreases alcohol intake in chronic alcoholics without harmful side-effects. Department of Pharmacology and School of Medicine,
Therapeutics,
Hospital Clinics,
JAIME M. MONTI
Montevideo, 11600 Uruguay
PAULO ALTERWAIN
Reyntjens A, Gelders IG, Hoppenbrowers ML, Vanden Bussche G. Thymosthenic effects of ritanserin (R 55667), a centrally acting serotonin-S2 receptor blocker. Drug Dev Res 1986, 8: 205-11. 2. Janssen PAJ The relevance of pharmacological studies to sleep research in psychiatry. Pharmacopsychiatry 1988; 21: 33-37 3. Naranjo CA, Sellers EM, Wu PH, Lawrin MO. Moderation of ethanol drinking: role of enhanced serotonergic neurotransmission In: Naranjo CA, Sellers EM, eds. Research advances m new psychopharmacological treatments for alcoholism 1.
Amsterdam: Elsevier, 1985: 171-86 1 Leon MB, Almagor Y, Erbel R, Teerstem PS, Perez Y, Schatz RA. Subacute thrombotic events after coronary stent placement clinical spectrum and predictive factors Circulation 1989, 80 (suppl II): 174 2. Pelzer H, Stuber W. Markers of hemostatic activation: new perspectives using immunochemical methods for determination of prothrombin fragment F1+ 2 and thrombin-antithrombin III complex. Thromb Haemostas 1989; 62: 165. 3 Ellis GE, Topul EJ Intracoronary stents: will they fulfil their promise as an adjunct to angioplasty? J Am Coll Cardiol 1989; 13: 1425-30. 4 Sigwart V, Urban PH, Golf S, et al Emergency stenting for acute occlusion after coronary balloon angioplasty. Circulation 1988; 78: 1121-27.
Ritanserin decreases alcohol intake in chronic alcoholics SIR,-Ritanserin is a potent and specific S-HT2-receptor antagonist. It increases slow-wave sleep (stages 3 and 4) in healthy volunteers, and when given to patients with dysthymic disorder reduces depressive mood states, insomnia, agitation, and anxiety .1,2 We have investigated the effects of ritanserin on mood and sleep in five male patients (mean age 43-8 [9.2] years) with a diagnosis of alcohol dependence (DSM III-R). In four patients the dependence was severe, whereas in the remaining one it was moderate. Patients were enrolled in the study after 30 days of abstinence. Ritanserin 10 mg daily was given in single blind fashion for 28 days, with placebo for 7 days before and for 15 days after ritanserin. No other drug was allowed during the study period, and patients were asked to abstain from drinking alcohol during both the placebo and ritanserin periods. The efficacy of ritanserin was measured by means of the Hamilton depression rating scale (HAMD), the Hamilton anxiety rating scale (HAMA) and the clinical global impression scale (CGI). In addition, polysomnographic recordings were done in the sleep laboratory at baseline and during ritanserin administration to assess its effect on sleep continuity and pattern. During ritanserin administration the mean total score with HAMD and HAMA showed a striking fall in all five patients. The patients’ condition as measured by CGI also improved. Furthermore, there was a consistent improvement of sleep continuity as judged by the decrease in the number of awakenings, total wake time, and wake time after sleep onset. Moreover, in sharp contrast to their behaviour before inclusion in the study, the five patients spontaneously reported after the first 3-7 days on ritanserin that they had no difficulty in curtailing their intake of alcohol. During the placebo period after ritanserin they felt no need or compulsion to drink when in the company of people who consumed spirits. No adverse effects were reported during ritanserin
CD14
as
marker for liver
allograft rejection?
SIR,—CD14 is a 55 kD glycoprotein, expressed chiefly on macrophages, and dendritic reticulum cells. CD14
monocytes,
to have a role in monocyte activation and signal transduction. 1-3 Immunostaining with CD 14 monoclonal antibody is very helpful in the histological diagnosis of renal allograft rejection and in its differentiation from other forms of interstitial nephritis.4 This prompted us to analyse the immunoreactivity of anti-CD 14 monoclonal antibodies LeuM3 (Becton-Dickinson) and WT14 (kindly provided by Dr M. J. J. T. Bogman) in 8 cases of liver allograft rejection (4 acute, 4 chronic), and to compare the staining pattern with that of 10 cases of acute and chronic hepatitis due to virus infection, autoimmunity, or drugs. Besides reactivity with sinusoidal lining cells, LeuM3 and WT14 revealed a honeycomb-like pattern of membrane staining on variously sized clusters of hepatocytes throughout the liver sample in 6 (4 acute, 2 chronic) of 8 cases of rejection, none of the 10 liver specimens with other causes of hepatitis displayed a similar hepatocellular staining. These preliminary results not only demonstrate for the first time the epithelial expression of CD 14 antigen, but also suggest that seems
of this myelomonocytic antigen is restricted to cases of liver allograft rejection. Immunostaining with anti-CD 14 may be a helpful tool in the histological diagnosis of liver
hepatocellular expression rejection.
Laboratory of Histo- and Cytochemistry, Department of Pathology, University Hospital Sint-Rafael, Catholic University of Leuven, B-3000 Leuven, Belgium
RICCARDO VOLPES JOOST J. VAN DEN OORD BOUDEWIJN VAN DAMME VALEER J. DESMET
Engagement of the monocyte surface antigen CD14 lymphocyte function-associated antigen-1/intercellular adhesion molecule-1-dependent homotypic adhesion J Immunol 1990; 145: 1394. 2 Lauener RP, Goyert SM, Geha RS, Vercilli D. Interleukin-4 downregulates CD14 expression on normal human monocytes. Eur J Immunol (in press). 3. Howell AL, Ball ED Induction of CD14 message in HL-60 promyclocytic leukemia cells and expression in cells from patients with acute myelogenous leukemia. Tissue Antigens 1989; 33: 198. 4 Bogman MJJT, Van de Winkel JGJ, Hoitsma AJ, et al Diagnosis of renal allograft rejection by macrophage immunostaining with a CD14 monoclonal antibody, 1. Lauener RP, Geha RS, Vercilli D.
induces
WT14. Lancet 1989; n. 238
CORRECTION
treatment.
Disulfiram and calcium carbimide have been widely used to deter alcohol intake; they inhibit the enzyme aldehyde dehydrogenase which metabolises acetaldehyde to acetic acid. As a result, ingestion
Armand Hammer. In Dr R. P. Gale’s obituary (Dec 22/29, p 1572) the beginning at the end of line 2 of the final paragraph should start: "He worked tirelessly... sentence
"
the presence of a thin layer of fibrin, some thrombus formation is essential for healing.3.4 The key reaction in the blood coagulation system cascade is the conversion of prothrombin to thrombin. During this process, factor Xa cleaves prothrombin, which results in the generation of both PTF and thrombin. In the presence of heparin, the serine protease can rapidly be neutralised by antithrombin III, which forms an inactive thrombin-antithrombin III complex (TAT). Both PTF and TAT can be regarded as molecular markers of a prethrombotic state .2 PTF is a useful marker that indicates an evolving subacute occlusion of the stented segment if concentrations are over 0-5 nmol/1. Dose reduction of heparin-even at therapeutic prothrombin time ratios-should therefore be avoided if PTF exceeds 0-5 nmol/1. HOLGER SWARS GERD HAFNER RAIMUND ERBEL WOLFRAM EHRENTHAL II Medical Clinic, HANS JÜRGEN RUPPRECHT and Institute of Clinical Chemistry, WINFRIED PRELLWITZ Johannes Gutenberg University, D 6500 Mainz 1, Germany JURGEN MEYER
of alcohol causes an accumulation of acetaldehyde and brings on nausea and vomiting. However, these drugs have disadvantages; the optimum dose and dosage schedule is not established, and they have adverse reactions and several contraindications with deleterious drug interactions.’ Zimeldine, which blocks serotonin uptake, decreased the daily intake of alcohol and increased the percentage of days of abstinence in chronic alcoholics.3However, the drug was withdrawn world wide because of reports of hepatitis and Guillain Barre syndrome. From these preliminary fmdings we conclude that ritanserin effectively decreases alcohol intake in chronic alcoholics without harmful side-effects. Department of Pharmacology and School of Medicine,
Therapeutics,
Hospital Clinics,
JAIME M. MONTI
Montevideo, 11600 Uruguay
PAULO ALTERWAIN
Reyntjens A, Gelders IG, Hoppenbrowers ML, Vanden Bussche G. Thymosthenic effects of ritanserin (R 55667), a centrally acting serotonin-S2 receptor blocker. Drug Dev Res 1986, 8: 205-11. 2. Janssen PAJ The relevance of pharmacological studies to sleep research in psychiatry. Pharmacopsychiatry 1988; 21: 33-37 3. Naranjo CA, Sellers EM, Wu PH, Lawrin MO. Moderation of ethanol drinking: role of enhanced serotonergic neurotransmission In: Naranjo CA, Sellers EM, eds. Research advances m new psychopharmacological treatments for alcoholism 1.
Amsterdam: Elsevier, 1985: 171-86 1 Leon MB, Almagor Y, Erbel R, Teerstem PS, Perez Y, Schatz RA. Subacute thrombotic events after coronary stent placement clinical spectrum and predictive factors Circulation 1989, 80 (suppl II): 174 2. Pelzer H, Stuber W. Markers of hemostatic activation: new perspectives using immunochemical methods for determination of prothrombin fragment F1+ 2 and thrombin-antithrombin III complex. Thromb Haemostas 1989; 62: 165. 3 Ellis GE, Topul EJ Intracoronary stents: will they fulfil their promise as an adjunct to angioplasty? J Am Coll Cardiol 1989; 13: 1425-30. 4 Sigwart V, Urban PH, Golf S, et al Emergency stenting for acute occlusion after coronary balloon angioplasty. Circulation 1988; 78: 1121-27.
Ritanserin decreases alcohol intake in chronic alcoholics SIR,-Ritanserin is a potent and specific S-HT2-receptor antagonist. It increases slow-wave sleep (stages 3 and 4) in healthy volunteers, and when given to patients with dysthymic disorder reduces depressive mood states, insomnia, agitation, and anxiety .1,2 We have investigated the effects of ritanserin on mood and sleep in five male patients (mean age 43-8 [9.2] years) with a diagnosis of alcohol dependence (DSM III-R). In four patients the dependence was severe, whereas in the remaining one it was moderate. Patients were enrolled in the study after 30 days of abstinence. Ritanserin 10 mg daily was given in single blind fashion for 28 days, with placebo for 7 days before and for 15 days after ritanserin. No other drug was allowed during the study period, and patients were asked to abstain from drinking alcohol during both the placebo and ritanserin periods. The efficacy of ritanserin was measured by means of the Hamilton depression rating scale (HAMD), the Hamilton anxiety rating scale (HAMA) and the clinical global impression scale (CGI). In addition, polysomnographic recordings were done in the sleep laboratory at baseline and during ritanserin administration to assess its effect on sleep continuity and pattern. During ritanserin administration the mean total score with HAMD and HAMA showed a striking fall in all five patients. The patients’ condition as measured by CGI also improved. Furthermore, there was a consistent improvement of sleep continuity as judged by the decrease in the number of awakenings, total wake time, and wake time after sleep onset. Moreover, in sharp contrast to their behaviour before inclusion in the study, the five patients spontaneously reported after the first 3-7 days on ritanserin that they had no difficulty in curtailing their intake of alcohol. During the placebo period after ritanserin they felt no need or compulsion to drink when in the company of people who consumed spirits. No adverse effects were reported during ritanserin
CD14
as
marker for liver
allograft rejection?
SIR,—CD14 is a 55 kD glycoprotein, expressed chiefly on macrophages, and dendritic reticulum cells. CD14
monocytes,
to have a role in monocyte activation and signal transduction. 1-3 Immunostaining with CD 14 monoclonal antibody is very helpful in the histological diagnosis of renal allograft rejection and in its differentiation from other forms of interstitial nephritis.4 This prompted us to analyse the immunoreactivity of anti-CD 14 monoclonal antibodies LeuM3 (Becton-Dickinson) and WT14 (kindly provided by Dr M. J. J. T. Bogman) in 8 cases of liver allograft rejection (4 acute, 4 chronic), and to compare the staining pattern with that of 10 cases of acute and chronic hepatitis due to virus infection, autoimmunity, or drugs. Besides reactivity with sinusoidal lining cells, LeuM3 and WT14 revealed a honeycomb-like pattern of membrane staining on variously sized clusters of hepatocytes throughout the liver sample in 6 (4 acute, 2 chronic) of 8 cases of rejection, none of the 10 liver specimens with other causes of hepatitis displayed a similar hepatocellular staining. These preliminary results not only demonstrate for the first time the epithelial expression of CD 14 antigen, but also suggest that seems
of this myelomonocytic antigen is restricted to cases of liver allograft rejection. Immunostaining with anti-CD 14 may be a helpful tool in the histological diagnosis of liver
hepatocellular expression rejection.
Laboratory of Histo- and Cytochemistry, Department of Pathology, University Hospital Sint-Rafael, Catholic University of Leuven, B-3000 Leuven, Belgium
RICCARDO VOLPES JOOST J. VAN DEN OORD BOUDEWIJN VAN DAMME VALEER J. DESMET
Engagement of the monocyte surface antigen CD14 lymphocyte function-associated antigen-1/intercellular adhesion molecule-1-dependent homotypic adhesion J Immunol 1990; 145: 1394. 2 Lauener RP, Goyert SM, Geha RS, Vercilli D. Interleukin-4 downregulates CD14 expression on normal human monocytes. Eur J Immunol (in press). 3. Howell AL, Ball ED Induction of CD14 message in HL-60 promyclocytic leukemia cells and expression in cells from patients with acute myelogenous leukemia. Tissue Antigens 1989; 33: 198. 4 Bogman MJJT, Van de Winkel JGJ, Hoitsma AJ, et al Diagnosis of renal allograft rejection by macrophage immunostaining with a CD14 monoclonal antibody, 1. Lauener RP, Geha RS, Vercilli D.
induces
WT14. Lancet 1989; n. 238
CORRECTION
treatment.
Disulfiram and calcium carbimide have been widely used to deter alcohol intake; they inhibit the enzyme aldehyde dehydrogenase which metabolises acetaldehyde to acetic acid. As a result, ingestion
Armand Hammer. In Dr R. P. Gale’s obituary (Dec 22/29, p 1572) the beginning at the end of line 2 of the final paragraph should start: "He worked tirelessly... sentence
"