270 method of electrophoresis of virus-specific proteins in polyacrylamide gels. Fig. 2 shows that that the drug in concentrations of 5-10 µg/ml sharply inhibits the synthesis of virus-specific proteins in MDCK cells. G. A. GALEGOV N. L. PUSHKARSKAYA N. R. SMIRNOVA -
Ivanovsky Institute of Virology, U.S.S.R. Academy of Medical Sciences,
D. I.
Moscow, 123098, U.S.S.R.
.
-
N. D. LVOV A. A. YATSINA V. M. ZHDANOV
BETA-BLOCKER WITHDRAWAL SYNDROME?
SIR The propranolol-withdrawal syndrome, which comprises ventricular arrhythmias, severe angina, myocardial infarction, and even death soon after sudden cessation of prowas first described in a series of case-reports and later confirmed in controlled clinical trials. To our knowledge the question whether cessation of therapy with other beta-blocking agents can also produce such a withdrawal syn:" drome is unsettled. We wish to point out the risk of rapid discontinuation of metoprolol therapy in patients with coronary heart-disease by reporting a case with typical withdrawal symptoms.
pranolol therapy,
A tions
with four previous myocardial infarcthis clinic for cardiac catheterisation. Coronary angiography revealed a 90% proximal left anterior descending coronary-artery stenosis, an 80% stenosis of the right coronary artery, and a 30-40% stenosis of the left circumflex coronary artery. The patient was treated with digoxin, phenprocoumon, triamterene, isosorbide dinitrate (3 x 20 mg three times a day) and metoprolol (100 mg twice a day). During this therapy the frequency of angina attacks was reduced to about one episode per week from 5-8 before treatment.
52-year-old was
man
admitted
SIR,-Legionella pneumophila, the aetiological agent of stains so lightly with Gram’s method that
legionnaires’ disease, it usually cannot be
seen
in Gram-stained sputum, transtra-
aspirate, pleural fluid, impression smears of tissue, or pathology sections. We have succeeded in staining legionellae in these materials using only the first dye in Gram’s procedure cheal
(ammonium-oxalate/crystal-violet). Even better results are obtained when we also use the second step of Gram’s procedure, Lugol’s iodine solution. After washing in water and drying, legionellx are seen as seemingly Gram-positive rods and threads. Seeing so many bacteria where before, with the complete Gram stain, none were seen, is startling (figs. 1 and 2). Direct immunofluorescent staining proves these bacteria to be legionelloc. As only the first two steps of the Gram procedure are needed, every bacteriological laboratory can instantly perform "half-a-Gram" when legionellæ are expected in clinical material and no bacteria are seen by the normal Gram stain. The new method is not specific for legionellm, but neither are the stains of Wolbachy-Giemsa or Dieterle. Hsemophili that have been overlooked in the Gram stain also show up clearly in "half-a-Gram". The new method does not replace direct
to
8 weeks later the patient was admitted to the thoracic surgery department (University of Frankfurt/Main) for a coronary bypass operation. During his preoperative stay metoprolol medication was abruptly discontinued and substituted by nifedipine (10 mg) while other drug therapy (except phenprocoumon) remained unchanged. Approximately 78 h after withdrawal of metoprolol he started to experience a dramatic worsening of his angina pectoris with up to three episodes of rest angina per day. On the fourth day after metoprolol withdrawal he experienced sudden onset of ventricular fibrillation; he was resuscitated by D.C. countershock. He subsequently had an anteroseptal myocardial reinfarction with typical clinical, electrocardiographic, and laboratory signs. During his stay in the coronary-care unit frequent premature ventricular contractions were observed and treated with intravenous lignocaine ( 1 .5g in 24 h) and disopyramide (200 mg three times a
EASY VISUALISATION OF LEGIONELLA PNEUMOPHILA BY "HALF-A-GRAM" STAIN PROCEDURE
Fig. 1—Legionellæ in impression smear of lung tissue, stained by Gram’s method, showing barely visible Gram-negative bacilli (reduced to 3/4 of x 1000).
day). Usually patients
with angina pectoris, who are admitted to a decrease in anginal symptoms with rest and reduced physical activity. In our patient, however, a pronounced increase of angina arid, subsequently, ventricular fibrillation with myocardial infarction was seen when metoprolol had been abruptly discontinued during the preoperative
hospital experience
period. This syndrome developing after sudden metoprolol withdrawal closely fits the spectrum of the so-called propranololwithdrawal syndrome. Thus, abrupt discontinuation of any beta-blocking agent should be expected to produce a withdrawal syndrome similar to that described for propranolol. THOMAS MEINERTZ
HANJÖRG JUST II Medizinische Universitätsklinik Mainz, D-6500 Mainz, West Germany
WOLFGANG KASPER FRIEDRICH KERSTING KARL-HEINZ BREUING
Fig. 2—Legionellæ in impression smear of same lung tissue, stained by "half-a-Gram". The single rods are pointed, 1.5-4 µm long, and may resemble pseudomonads, while many are coccoid and some are in threads (reduced to 3/4 of x 1000).
271 immunofluorescent staining which antigen ofL. pneumophila. Direct fluorescent antiserum
was
specifically recognises
the
kindly provided by the Center for
Disease Control, Atlanta, Georgia, U.S.A.
Rijksinstituut voor de Volksgezondheid, Bilthoven, Netherlands
J. L. DE FREITAS J. BORST
Department of Infectious Diseases, University Hospital, Leiden
P. L. MEENHORST
characteristics is most readily seen in high-tension electrical injury of an extremity, where non-viable muscle near the centrally located bone may underlie more superficial viable muscle and the extent of skin injury at the contact points offers little indication of the actual extent of trauma. This situation demands thorough surgical examination of the extremity, particularly of the periosseous muscles, to determine the extent of debridement or amputation necessary. Army Institute of Surgical Research, Brooke Army Medical Center,
U.S.
LEGIONELLA PNEUMOPHILA SEROTYPES to our paper on the isolation of a serotype of Legionella pneumophila (Dec. 2), we reported a preliminary finding regarding the stability of cellular antigens of the Los Angeles 1 serotype in formalin. I have been unable to duplicate this experiment, and now concur with Center for Disease Control investigators that prolonged formalin fixation of this strain does not alter its reactivity with either homologous or heterologous antisera.
SIR,-In the addendum
Fort Sam Houston, Texas 78234, U.S.A.
BASIL A. PRUITT, JR ARTHUR D. MASON, JR
FIBRE AND DIABETES
new
Division of Infectious Diseases, V. A. Wadsworth Medical Center, Los Angeles, California 90073, U.S.A.
PAUL EDELSTEIN
LEGIONNAIRES’ DISEASE AND CEREBRAL DISTURBANCE
SiR,—The difficulty of establishing a diagnosis of legionnaires’ disease solely on serological tests have been the subject of recent editorial comments.’,2 Consequently, sporadic instances of patients with unexplained pulmonary infiltrates represent a diagnostic dilemma. The patients described by Dr Lees and Dr Tyrrell (Dec. 23/30) could very well not have had legionnaires’ disease. The legionnaires’ bacillus has been successfully isolated from a transtracheal aspirate.’ Thus without cultural confirmation, Lees and Tyrell have not established the diagnosis of legionnaires’ disease. The diagnosis in the second reported patient was based initially on clinical response to erythromycin; such reasoning is untenable. Department of Infectious Diseases, Geisinger Medical Center, Danville, Pennsylvania 17821, U.S.A.
GARY R. PLOTKIN
HIGH-TENSION ELECTRICAL INJURY
SIR,-Your editorial4 properly emphasises the risk of deep tissue damage in patients with high-tension electrical injury, but the mechanism of that damage appears to be related more to the configuration of the tissue involved than to its resistarice properties. In high-voltage trauma, heat is the principal mediator of tissue injury; the differences of tissue resistance are so small that the body acts as a volume conductor. Heat is generated in this conductor as a function of voltage drop and current flow per unit cross-sectional area, or current density. This dependence upon cross-sectional area accounts for the frequency of severe injury to the extremities and the rarity of major injury to the trunk in high-tension electrical injury. At the points of contact, where density is greatest, the skin is severely injured and chars; when this occurs resistance rises sharply, limiting further passage of current and heating. The heated conductor cools, the deeper portions cooling more slowly than the superficial. Since thermal injury of tissue is dependent upon both the temperature achieved and the duration of exposure to that temperature, the deeper tissues are more liable to severe injury. The clinical reflection of these 1 British Medical Journal, 1978, ii, 1319. 2 Tsai T. F., Fraser, D. W. Ann. intern. Med, 1978, 89, 413. 3 Lattimer, G. L., McCrone, C., Galgon, J. New Engl. J. 1172.
4 Lancet, 1978, ii, 978.
Med.
1978, 299,
SIR,-Mr Wolever and colleagues have reported
on the the reducequivalent gelled non-gelled guar tion in post-prandial blood-glucose in healthy volunteers given an oral glucose load. We have been investigating the properties of several fibre compounds taken in powder form by diabetics, and as part of this study we compared the effects of guar and pectin taken in gelled and non-gelled forms. There was little difference in the effect on post-prandial glucose between 10 g guar taken in an adequately hydrated form as a blancmange and a similar dose taken in powder form. However, the meal supplied on both occasions to our subjects consisted of food items often consumed for breakfast-i.e., cornflakes (30 g), milk (200 ml), bread (35 g), butter (8 g), marmalade (25 g), tea (150 ml), and sugar (15 g). The use of normal meals is a more appropriate test of the likely effect of fibre when added to normal diets for diabetics; the addition, to a liquid test meal, of any substance, even of non-fibre origin, might affect plasmaglucose if it delayed gastric emptying and slowed glucose
effects of
and
on
absorption. Not only was the effect of gelling unimportant but the effect of the guar as such was unremarkable (see figure). Although some reduction in plasma-glucose seems to have been achieved, this reduction was not, in our subjects, statistically significant, and we doubt whether the effect in many other trials23 can be claimed to be therapeutically relevant. This limited response does not mean that dietary fibre given in a different form will not be effective, but the demonstration in diabetics that glycosuria can be reduced during a trial period with extra dietary fibre23 cannot be taken as proof that the 1. Wolever, T. M. S., Taylor, R., Goff, D. V. Lancet, 1978, ii, 1381. 2. Jenkins, D. J. A., and others. ibid. 1977, ii, 779. 3. Jenkins, D. J. A., and others. Br. med. J. 1978, ii,1744.
Increment in post-prandial plasma-glucose in four maturityonset diabetics after test breakfast supplemented with 10 g gelled or non-gelled guar.
Ivanovsky Institute of Virology, U.S.S.R. Academy of Medical Sciences,
D. I.
Moscow, 123098, U.S.S.R.
.
-
N. D. LVOV A. A. YATSINA V. M. ZHDANOV
BETA-BLOCKER WITHDRAWAL SYNDROME?
SIR The propranolol-withdrawal syndrome, which comprises ventricular arrhythmias, severe angina, myocardial infarction, and even death soon after sudden cessation of prowas first described in a series of case-reports and later confirmed in controlled clinical trials. To our knowledge the question whether cessation of therapy with other beta-blocking agents can also produce such a withdrawal syn:" drome is unsettled. We wish to point out the risk of rapid discontinuation of metoprolol therapy in patients with coronary heart-disease by reporting a case with typical withdrawal symptoms.
pranolol therapy,
A tions
with four previous myocardial infarcthis clinic for cardiac catheterisation. Coronary angiography revealed a 90% proximal left anterior descending coronary-artery stenosis, an 80% stenosis of the right coronary artery, and a 30-40% stenosis of the left circumflex coronary artery. The patient was treated with digoxin, phenprocoumon, triamterene, isosorbide dinitrate (3 x 20 mg three times a day) and metoprolol (100 mg twice a day). During this therapy the frequency of angina attacks was reduced to about one episode per week from 5-8 before treatment.
52-year-old was
man
admitted
SIR,-Legionella pneumophila, the aetiological agent of stains so lightly with Gram’s method that
legionnaires’ disease, it usually cannot be
seen
in Gram-stained sputum, transtra-
aspirate, pleural fluid, impression smears of tissue, or pathology sections. We have succeeded in staining legionellae in these materials using only the first dye in Gram’s procedure cheal
(ammonium-oxalate/crystal-violet). Even better results are obtained when we also use the second step of Gram’s procedure, Lugol’s iodine solution. After washing in water and drying, legionellx are seen as seemingly Gram-positive rods and threads. Seeing so many bacteria where before, with the complete Gram stain, none were seen, is startling (figs. 1 and 2). Direct immunofluorescent staining proves these bacteria to be legionelloc. As only the first two steps of the Gram procedure are needed, every bacteriological laboratory can instantly perform "half-a-Gram" when legionellæ are expected in clinical material and no bacteria are seen by the normal Gram stain. The new method is not specific for legionellm, but neither are the stains of Wolbachy-Giemsa or Dieterle. Hsemophili that have been overlooked in the Gram stain also show up clearly in "half-a-Gram". The new method does not replace direct
to
8 weeks later the patient was admitted to the thoracic surgery department (University of Frankfurt/Main) for a coronary bypass operation. During his preoperative stay metoprolol medication was abruptly discontinued and substituted by nifedipine (10 mg) while other drug therapy (except phenprocoumon) remained unchanged. Approximately 78 h after withdrawal of metoprolol he started to experience a dramatic worsening of his angina pectoris with up to three episodes of rest angina per day. On the fourth day after metoprolol withdrawal he experienced sudden onset of ventricular fibrillation; he was resuscitated by D.C. countershock. He subsequently had an anteroseptal myocardial reinfarction with typical clinical, electrocardiographic, and laboratory signs. During his stay in the coronary-care unit frequent premature ventricular contractions were observed and treated with intravenous lignocaine ( 1 .5g in 24 h) and disopyramide (200 mg three times a
EASY VISUALISATION OF LEGIONELLA PNEUMOPHILA BY "HALF-A-GRAM" STAIN PROCEDURE
Fig. 1—Legionellæ in impression smear of lung tissue, stained by Gram’s method, showing barely visible Gram-negative bacilli (reduced to 3/4 of x 1000).
day). Usually patients
with angina pectoris, who are admitted to a decrease in anginal symptoms with rest and reduced physical activity. In our patient, however, a pronounced increase of angina arid, subsequently, ventricular fibrillation with myocardial infarction was seen when metoprolol had been abruptly discontinued during the preoperative
hospital experience
period. This syndrome developing after sudden metoprolol withdrawal closely fits the spectrum of the so-called propranololwithdrawal syndrome. Thus, abrupt discontinuation of any beta-blocking agent should be expected to produce a withdrawal syndrome similar to that described for propranolol. THOMAS MEINERTZ
HANJÖRG JUST II Medizinische Universitätsklinik Mainz, D-6500 Mainz, West Germany
WOLFGANG KASPER FRIEDRICH KERSTING KARL-HEINZ BREUING
Fig. 2—Legionellæ in impression smear of same lung tissue, stained by "half-a-Gram". The single rods are pointed, 1.5-4 µm long, and may resemble pseudomonads, while many are coccoid and some are in threads (reduced to 3/4 of x 1000).
271 immunofluorescent staining which antigen ofL. pneumophila. Direct fluorescent antiserum
was
specifically recognises
the
kindly provided by the Center for
Disease Control, Atlanta, Georgia, U.S.A.
Rijksinstituut voor de Volksgezondheid, Bilthoven, Netherlands
J. L. DE FREITAS J. BORST
Department of Infectious Diseases, University Hospital, Leiden
P. L. MEENHORST
characteristics is most readily seen in high-tension electrical injury of an extremity, where non-viable muscle near the centrally located bone may underlie more superficial viable muscle and the extent of skin injury at the contact points offers little indication of the actual extent of trauma. This situation demands thorough surgical examination of the extremity, particularly of the periosseous muscles, to determine the extent of debridement or amputation necessary. Army Institute of Surgical Research, Brooke Army Medical Center,
U.S.
LEGIONELLA PNEUMOPHILA SEROTYPES to our paper on the isolation of a serotype of Legionella pneumophila (Dec. 2), we reported a preliminary finding regarding the stability of cellular antigens of the Los Angeles 1 serotype in formalin. I have been unable to duplicate this experiment, and now concur with Center for Disease Control investigators that prolonged formalin fixation of this strain does not alter its reactivity with either homologous or heterologous antisera.
SIR,-In the addendum
Fort Sam Houston, Texas 78234, U.S.A.
BASIL A. PRUITT, JR ARTHUR D. MASON, JR
FIBRE AND DIABETES
new
Division of Infectious Diseases, V. A. Wadsworth Medical Center, Los Angeles, California 90073, U.S.A.
PAUL EDELSTEIN
LEGIONNAIRES’ DISEASE AND CEREBRAL DISTURBANCE
SiR,—The difficulty of establishing a diagnosis of legionnaires’ disease solely on serological tests have been the subject of recent editorial comments.’,2 Consequently, sporadic instances of patients with unexplained pulmonary infiltrates represent a diagnostic dilemma. The patients described by Dr Lees and Dr Tyrrell (Dec. 23/30) could very well not have had legionnaires’ disease. The legionnaires’ bacillus has been successfully isolated from a transtracheal aspirate.’ Thus without cultural confirmation, Lees and Tyrell have not established the diagnosis of legionnaires’ disease. The diagnosis in the second reported patient was based initially on clinical response to erythromycin; such reasoning is untenable. Department of Infectious Diseases, Geisinger Medical Center, Danville, Pennsylvania 17821, U.S.A.
GARY R. PLOTKIN
HIGH-TENSION ELECTRICAL INJURY
SIR,-Your editorial4 properly emphasises the risk of deep tissue damage in patients with high-tension electrical injury, but the mechanism of that damage appears to be related more to the configuration of the tissue involved than to its resistarice properties. In high-voltage trauma, heat is the principal mediator of tissue injury; the differences of tissue resistance are so small that the body acts as a volume conductor. Heat is generated in this conductor as a function of voltage drop and current flow per unit cross-sectional area, or current density. This dependence upon cross-sectional area accounts for the frequency of severe injury to the extremities and the rarity of major injury to the trunk in high-tension electrical injury. At the points of contact, where density is greatest, the skin is severely injured and chars; when this occurs resistance rises sharply, limiting further passage of current and heating. The heated conductor cools, the deeper portions cooling more slowly than the superficial. Since thermal injury of tissue is dependent upon both the temperature achieved and the duration of exposure to that temperature, the deeper tissues are more liable to severe injury. The clinical reflection of these 1 British Medical Journal, 1978, ii, 1319. 2 Tsai T. F., Fraser, D. W. Ann. intern. Med, 1978, 89, 413. 3 Lattimer, G. L., McCrone, C., Galgon, J. New Engl. J. 1172.
4 Lancet, 1978, ii, 978.
Med.
1978, 299,
SIR,-Mr Wolever and colleagues have reported
on the the reducequivalent gelled non-gelled guar tion in post-prandial blood-glucose in healthy volunteers given an oral glucose load. We have been investigating the properties of several fibre compounds taken in powder form by diabetics, and as part of this study we compared the effects of guar and pectin taken in gelled and non-gelled forms. There was little difference in the effect on post-prandial glucose between 10 g guar taken in an adequately hydrated form as a blancmange and a similar dose taken in powder form. However, the meal supplied on both occasions to our subjects consisted of food items often consumed for breakfast-i.e., cornflakes (30 g), milk (200 ml), bread (35 g), butter (8 g), marmalade (25 g), tea (150 ml), and sugar (15 g). The use of normal meals is a more appropriate test of the likely effect of fibre when added to normal diets for diabetics; the addition, to a liquid test meal, of any substance, even of non-fibre origin, might affect plasmaglucose if it delayed gastric emptying and slowed glucose
effects of
and
on
absorption. Not only was the effect of gelling unimportant but the effect of the guar as such was unremarkable (see figure). Although some reduction in plasma-glucose seems to have been achieved, this reduction was not, in our subjects, statistically significant, and we doubt whether the effect in many other trials23 can be claimed to be therapeutically relevant. This limited response does not mean that dietary fibre given in a different form will not be effective, but the demonstration in diabetics that glycosuria can be reduced during a trial period with extra dietary fibre23 cannot be taken as proof that the 1. Wolever, T. M. S., Taylor, R., Goff, D. V. Lancet, 1978, ii, 1381. 2. Jenkins, D. J. A., and others. ibid. 1977, ii, 779. 3. Jenkins, D. J. A., and others. Br. med. J. 1978, ii,1744.
Increment in post-prandial plasma-glucose in four maturityonset diabetics after test breakfast supplemented with 10 g gelled or non-gelled guar.
