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UROKINASE IN THROMBOEMBOLIC DISEASE
420 who refer
Hardisty and Huttonfor " a good description of for all these tests " will be sadly disappointedtechniques though they will find references to the original descriptions of some of them. Department of Hæmatology, to
The Hospital for Sick Children, Great Ormond Street, London W.C.1.
R. M. HARDISTY.
UROKINASE IN THROMBOEMBOLIC DISEASE SiR,—Your annotation (Jan. 27, p. 189) states that " Neither trial disclosed toxic reactions to urokinase " during treatment of pulmonary embolism. 1In the first trial, the authors pointed out that all 13 patients " exhibited a mild to moderate degree of oozing of blood from the venipuncture sites; moderate pressure had to be applied to maintain hemostasis". In addition, 1 patient acquired a hxmatoma at a femoral puncture-site and another had bleeding gums and haEmatemesis, each required transfusion of 1 litre of blood. In the second trial (8 patients), the authors observed in 1 patient a fatal syndrome of purpura with extensive haemorrhage and perforation of the bowel. A third report,3 not mentioned in the annotation, indicated that 9 of 10 patients had oozing of blood from fresh cut-down sites and that 5 became anaemic (haemoglobin fell to 10-5 g. or lower) during infusion of urokinase. The occurrence of bleeding during treatment with urokinase is not unexpected in view of the recognised anticoagulative effect of thrombolytic substances,4and perhaps bleeding induced by urokinase should be considered a sideeffect rather than a toxic reaction. Nevertheless, it seems appropriate to recognise bleeding as a potentially serious complication of treatment with urokinase. Laboratory of Experimental Cardiology, St. Luke’s Hospital Center, New York, New York 10025.
RICHARD S. CRAMPTON.
BONE-MARROW CULTURE IN INFECTIOUS DISEASES to Dr. Garcia’s query (Jan. 6, p. 52) SIR,-In response regarding the culture of bone-marrow blood in infectious
diseases, not only is this a painful procedure, but our experience suggests that it is
a
singularly unrewarding routine method of
study. RECOVERY
OF
BACTERIAL AGENTS FROM BLOOD AND CULTURES IN 123 PATIENTS
BONE-MARROW
We studied 300 bone-marrow aspirations. These were cultured for bacteria, Mycoplasma spp., and L-forms, and only 1 significant isolation was madc--Staphylococcus aureus. (Recovery of Staph. epidermidis from one aspirate was not D. W., Wagner, H. N., Jr., Holmes, R. A. New Engl. J. Med. 1967, 277, 1161. 2. Sasahara, A. A., Cannilla, J. E., Belki, J. S., Morse, R. L., Criss, A. J. ibid. p. 1168. 3. Sautter, R. D., Emanuel, D. A., Fletcher, F. W., Wenzel, F. J., Matson, J. I. J. Am. med. Ass. 1967, 202, 215. 4. Fletcher, A. P., Alkjaersig, N., Sherry, S. J. clin. Invest. 1962, 41, 896.
1.
Tow,
considered to be a significant isolation.) This is an incidence of only 0-3%. In the same group of patients, 123 had one or more blood-cultures. There were 9 significant isolations-an incidence of 7-3%. (Staph. epidermidis and Bacillus spp. were not considered to be significant isolations; if included, the incidence would be 11-4%.) Approximately a third of the marrow aspirations were in patients with disorders variously reported as associated with positive cultures. Culture evidence proved bacterial infection in 25, with bactersmia in 8. The comparison of blood and bone-marrow cultures in 123 patients is shown in the accompanying table. Because of such findings, we have concluded that bonemarrow culture is of limited value in the isolation of infectious agents. In most infected patients, blood-cultures are far more likely to be positive than bone-marrow cultures. However, a small percentage of bone-marrow cultures may yield positive results when other culture specimens are negative, as in our " " single case. Thus, as a routine, myeloculture seems to be of extremely limited value. We feel that it should be performed only when there is a strong clinical impression of an infectious condition, with other bacteriological findings negative. Division of Clinical Pathology, CHARLES L. JOHNSTON, Jr. Medical College of Virginia, HARRY P. DALTON. Richmond, Virginia 23219.
DYSGAMMAGLOBULINÆMIA TYPE IV SIR,-Dr. Hobbs (Jan. 20, p. 110) gives evidence for an immune imbalance in dysgammaglobulinmmia type iv; he also reports that the cellular immune system is normal in this type of dysgammaglobulinasmia except for that associated with ataxia telangiectasia, in which case it is suggested that the cellular immune defect occurs only late in the disease. We describe here a patient with dysgammaglobulinasmia type IV and an associated deficiency in cellular immunity who exhibited no evidence of ataxia telangiectasia. The patient, a 24-year-old man, was admitted here on Aug. 27, 1967, for evaluation of bronchiectasis. Since aged 3 or 4 months, he had had recurrent episodes of bronchitis, asthma, and sinusitis, and four episodes of pneumonia. Since early childhood he had had classic chronic atopic dermatitis and in 1967, for the first time, he had had ragweed hay fever. The patient’s parents were first cousins and " allergies " are prevalent on both sides of the family. He showed typical findings of obstructive airway disease, along with mild chronic atopic dermatitis and clubbed finger-nails. He was mentally retarded but there was no neurological abnormality and there were no telangiectasias. Lymph-nodes were spotty and small, and the liver and spleen were not palpable. Chest X-ray findings were interpreted as compatible with bilateral lowerlobe bronchiectasis. Serum-protein paper electrophoresis was normal, but IgA was absent, IgG normal (1200 and 1500 mg. per 100 ml.), and IgM slightly diminished (30 and 42 mg. per 100 ml.) (Hyland Laboratories Immunoplates). Isohsmagglutinin titres were: anti-A 1/32, anti-B 1/32. Full immunisation with typhoid antigen produced titres of 1/80 (typhoid H) and 1/160 (typhoid 0) three weeks after the last dose. A Schick test was negative. Skin-sensitising antibody was present to many inhalant antigens. Complete gastrointestinal evaluation, including full X-ray series and tests of malabsorption, was normal. Evaluation of the cellular immune system also revealed a deficiency. Purified-protein-derivative (intermediate), histoplasmin, and Candida albicans 1/100 (0.1 ml.), skin tests were negative (over 90% of normal adults showed delayed hypersensitivity to the last-named antigen 1). A mumps skin test was negative, although the patient’s mother stated he had had mumps as a child. A full-thickness skin allograft from his stepfather remained in place for 30 days without eliciting a classic graft rejection. Multiple biopsies of the graft and graftbed showed no evidence of mononuclear cellular infiltration. The graft appeared to be " resorbed ", and the final biopsy 1.
Shannon, D. C., Johnson, G., Rosen, F. S., Austen, K. F. New Engl. J. Med. 1966, 275, 690.
Hardisty and Huttonfor " a good description of for all these tests " will be sadly disappointedtechniques though they will find references to the original descriptions of some of them. Department of Hæmatology, to
The Hospital for Sick Children, Great Ormond Street, London W.C.1.
R. M. HARDISTY.
UROKINASE IN THROMBOEMBOLIC DISEASE SiR,—Your annotation (Jan. 27, p. 189) states that " Neither trial disclosed toxic reactions to urokinase " during treatment of pulmonary embolism. 1In the first trial, the authors pointed out that all 13 patients " exhibited a mild to moderate degree of oozing of blood from the venipuncture sites; moderate pressure had to be applied to maintain hemostasis". In addition, 1 patient acquired a hxmatoma at a femoral puncture-site and another had bleeding gums and haEmatemesis, each required transfusion of 1 litre of blood. In the second trial (8 patients), the authors observed in 1 patient a fatal syndrome of purpura with extensive haemorrhage and perforation of the bowel. A third report,3 not mentioned in the annotation, indicated that 9 of 10 patients had oozing of blood from fresh cut-down sites and that 5 became anaemic (haemoglobin fell to 10-5 g. or lower) during infusion of urokinase. The occurrence of bleeding during treatment with urokinase is not unexpected in view of the recognised anticoagulative effect of thrombolytic substances,4and perhaps bleeding induced by urokinase should be considered a sideeffect rather than a toxic reaction. Nevertheless, it seems appropriate to recognise bleeding as a potentially serious complication of treatment with urokinase. Laboratory of Experimental Cardiology, St. Luke’s Hospital Center, New York, New York 10025.
RICHARD S. CRAMPTON.
BONE-MARROW CULTURE IN INFECTIOUS DISEASES to Dr. Garcia’s query (Jan. 6, p. 52) SIR,-In response regarding the culture of bone-marrow blood in infectious
diseases, not only is this a painful procedure, but our experience suggests that it is
a
singularly unrewarding routine method of
study. RECOVERY
OF
BACTERIAL AGENTS FROM BLOOD AND CULTURES IN 123 PATIENTS
BONE-MARROW
We studied 300 bone-marrow aspirations. These were cultured for bacteria, Mycoplasma spp., and L-forms, and only 1 significant isolation was madc--Staphylococcus aureus. (Recovery of Staph. epidermidis from one aspirate was not D. W., Wagner, H. N., Jr., Holmes, R. A. New Engl. J. Med. 1967, 277, 1161. 2. Sasahara, A. A., Cannilla, J. E., Belki, J. S., Morse, R. L., Criss, A. J. ibid. p. 1168. 3. Sautter, R. D., Emanuel, D. A., Fletcher, F. W., Wenzel, F. J., Matson, J. I. J. Am. med. Ass. 1967, 202, 215. 4. Fletcher, A. P., Alkjaersig, N., Sherry, S. J. clin. Invest. 1962, 41, 896.
1.
Tow,
considered to be a significant isolation.) This is an incidence of only 0-3%. In the same group of patients, 123 had one or more blood-cultures. There were 9 significant isolations-an incidence of 7-3%. (Staph. epidermidis and Bacillus spp. were not considered to be significant isolations; if included, the incidence would be 11-4%.) Approximately a third of the marrow aspirations were in patients with disorders variously reported as associated with positive cultures. Culture evidence proved bacterial infection in 25, with bactersmia in 8. The comparison of blood and bone-marrow cultures in 123 patients is shown in the accompanying table. Because of such findings, we have concluded that bonemarrow culture is of limited value in the isolation of infectious agents. In most infected patients, blood-cultures are far more likely to be positive than bone-marrow cultures. However, a small percentage of bone-marrow cultures may yield positive results when other culture specimens are negative, as in our " " single case. Thus, as a routine, myeloculture seems to be of extremely limited value. We feel that it should be performed only when there is a strong clinical impression of an infectious condition, with other bacteriological findings negative. Division of Clinical Pathology, CHARLES L. JOHNSTON, Jr. Medical College of Virginia, HARRY P. DALTON. Richmond, Virginia 23219.
DYSGAMMAGLOBULINÆMIA TYPE IV SIR,-Dr. Hobbs (Jan. 20, p. 110) gives evidence for an immune imbalance in dysgammaglobulinmmia type iv; he also reports that the cellular immune system is normal in this type of dysgammaglobulinasmia except for that associated with ataxia telangiectasia, in which case it is suggested that the cellular immune defect occurs only late in the disease. We describe here a patient with dysgammaglobulinasmia type IV and an associated deficiency in cellular immunity who exhibited no evidence of ataxia telangiectasia. The patient, a 24-year-old man, was admitted here on Aug. 27, 1967, for evaluation of bronchiectasis. Since aged 3 or 4 months, he had had recurrent episodes of bronchitis, asthma, and sinusitis, and four episodes of pneumonia. Since early childhood he had had classic chronic atopic dermatitis and in 1967, for the first time, he had had ragweed hay fever. The patient’s parents were first cousins and " allergies " are prevalent on both sides of the family. He showed typical findings of obstructive airway disease, along with mild chronic atopic dermatitis and clubbed finger-nails. He was mentally retarded but there was no neurological abnormality and there were no telangiectasias. Lymph-nodes were spotty and small, and the liver and spleen were not palpable. Chest X-ray findings were interpreted as compatible with bilateral lowerlobe bronchiectasis. Serum-protein paper electrophoresis was normal, but IgA was absent, IgG normal (1200 and 1500 mg. per 100 ml.), and IgM slightly diminished (30 and 42 mg. per 100 ml.) (Hyland Laboratories Immunoplates). Isohsmagglutinin titres were: anti-A 1/32, anti-B 1/32. Full immunisation with typhoid antigen produced titres of 1/80 (typhoid H) and 1/160 (typhoid 0) three weeks after the last dose. A Schick test was negative. Skin-sensitising antibody was present to many inhalant antigens. Complete gastrointestinal evaluation, including full X-ray series and tests of malabsorption, was normal. Evaluation of the cellular immune system also revealed a deficiency. Purified-protein-derivative (intermediate), histoplasmin, and Candida albicans 1/100 (0.1 ml.), skin tests were negative (over 90% of normal adults showed delayed hypersensitivity to the last-named antigen 1). A mumps skin test was negative, although the patient’s mother stated he had had mumps as a child. A full-thickness skin allograft from his stepfather remained in place for 30 days without eliciting a classic graft rejection. Multiple biopsies of the graft and graftbed showed no evidence of mononuclear cellular infiltration. The graft appeared to be " resorbed ", and the final biopsy 1.
Shannon, D. C., Johnson, G., Rosen, F. S., Austen, K. F. New Engl. J. Med. 1966, 275, 690.