- Email: [email protected]
Anaphylaxis due to hydroxyethyl-starch-reactive antibodies
carbohydrate prosthetic groups was not detected. These Gly m I and HPS are essentially the same but post-translationally processed in a different way, protein further studies are needed for clarification. although HPS is a member of a new family of cysteine-rich proteins. The members of this family show a pattern of eight cysteine residues which form four disulphide bridges similar to several non-specific lipid-transfer proteins. However, the biological function of HPS has not yet been identified. The tridimensional structure of HPS has been determined by Xfacts suggest that
ray diffraction methods.5 The molecule is a four-helix bundle formed by two antiparallel helix sets, which together with the
connecting loops and a &bgr;-strand form a spiral so that the final surface is similar to that found in proteins of much lower hydrophobicity. This may explain why the protein is easily released from soybean hull dust, and how it can permeate the mucosal membranes of the respiratory tract to produce asthmatic reactions. Our findings indicate that Gly m I is a valuable model to study the mechanism of the human allergic response. The availability of detailed structural information on HPS, and therefore Gly m I, will facilitate the definition of the B-cell and T-cell epitopes involved in the immune response to this allergen. Such knowledge might lead to more effective treatment for these allergies. This
study was supported by Alergia e Inmunologia Abello SA
*R Gonzalez, J Varela, J Carreira, F Polo *Dipartimento Investigación, Alergia e Inmunologia Abelló SA, 19. 28037 Madrid, Spain; and Centro de Investigaciones Biológicas, CSIC Antó JM, Sunyer J, Rodriguez-Roisin R, Suárez-Cervera M, Vázquez L. The Toxicoepidemiological Committee. Community outbreaks of asthma associated with inhalation of soybean dust. N Engl J Med 1989; 320: 1097-102. 2 González R, Zapatero L, Caravaca F, Carreira J. Identification of soybean proteins responsible for respiratory allergies. Int Arch Allergy Appl Immunol 1991; 95: 53-57. 3 González R, Polo F, Zapatero L, Caravaca F, Carreira J. Purification and characterization of major inhalant allergens from soybean hulls. Clin Exp Allergy 1992; 22: 748-55. 4 Odani S, Koide T, Ono T, Seto Y, Tanaka T. Soybean hydrophobic protein: isolation, partial characterization and the complete primary structure. Eur J Biochem 1987; 162: 485-91. 5 Baud F, Pebay-Peyroula E, Cohen-Addad C, Odani S, Lehmann MS. Crystal structure of hydrophobic protein from soybean; a member of a new cysteine-rich family. J Mol Biol 1993; 231: 877-87. 1
Anaphylaxis due to hydroxyethyl-starchreactive antibodies SiR-Colloids are routinely used for primary resuscitation from hypovolaemia and shock and for perioperative fluid management. Synthetic colloids such as dextran or hydroxyethyl starch (HES) improve microcirculatory blood flow and are less expensive than human albumin. However, adverse reactions such as flush, urticaria, hypotension, shock, and even cardiac arrest have been reported for all plasma substitutes in clinical use. An involvement of specific antibodies directed against the colloid eliciting the adverse reaction has been proven for dextran. The naturally occurring dextran-reactive antibodies predominantly belong to the IgG class. With implementation of the hapten prophylaxis (preinjection of 20 mL dextran 1) the incidence of severe dextran-induced anaphylactic reactions for all infusions given was reduced from 0.022% reported between 1975 and 1979 to 0-001% in the years 1983-85.’ By contrast, the exact mechanisms underlying the adverse reactions observed after HES administration are unknown, since preformed antibodies against HES have not been demonstrated so far, even when the highly sensitive ELISA technique was used.2
underwent surgery for an infrarenal History included leucocytosis with absolute hypereosinophilia, and an area of hypoperfusion in the posterior myocardial wall, suggesting an old non-transmural infarction. Induction of anaesthesia was uneventful, and all haemodynamic indices were stable until cross-clamping of the aorta. After clamping blood pressure decreased and pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP) were low (mean arterial pressure [MAP] from 93 to 63 mm Hg; PCWP 5 mm Hg, CVP 2 mm Hg). Therefore intravenous infusion of hyperosmolar HES 10% (molecular weight 200 000/0-5) plus crystalloid solution was started. Within 2 min (after only 20 mL HES) the heart rate dropped from 90 to 45 beats per min and MAP reached 45 mm Hg; at this point cardiac output was 1-8 LJmin (6-0 L/min before clamping of the aorta). Intravenous dopamine was set to 40 mg/h; however, atropine 0-5 mg and adrenaline 0-5 mg had to be administered to normalise the heart rate and raise perfusion pressure to 90 mm Hg. Because PCWP remained low (2 mm Hg), a further 1 L of iso-osmolar HES 10% was infused together with 1 L of crystalloid solution. Since serum concentrations of potassium and haemoglobin as well as blood gas analysis were normal, acute myocardial failure or reinfarction (as a result of increased afterload by crossclamping of the aorta) was assumed. To stabilise haemodynamic indices a total of 1-5 mg adrenaline, 20 mg dopamine, and 2 L of crystalloids were administered, achieving a PCWP of 7 mm Hg. 5 min after declamping, cardiac output amounted to 10.7 L/min, MAP 70 mm Hg, and PCWP 11 mm Hg. The operation was successfully completed and the patient transferred to the intensive-care unit, where he quickly recovered. Compared with a all preoperative electrocardiogram, postoperative electrocardiograms were unchanged and there were no increases in serum creatinine kinase (CK) or CK-MB. Blood samples obtained from the arterial line 10 min after the event were analysed for the presence of HES-reactive antibodies with ELISA. The results were compared with titres measured in serum sampled the day before operation (table). The decrease of HES-specific immunoglobulin titres reflects consumption of antibodies induced by administration of the antigen-ie, HES. This view is supported by the persistent increase in antibody concentration of all immunoglobulin classes except IgE over the following weeks. To our knowledge, the ELISA used is not influenced by the pre-existing absolute eosinophilia of unknown origin. In our patient for the first time high titres of HES-specific antibodies were detected in serum at the time of reaction. Their concentration sharply decreased after giving 1 L of HES. Reappearance of these immunoglobulins, particularly of the IgG class, was observed during the following weeks (table). The neutralisation of antibody titres upon exposure to HES and reappearance of specific antibodies within 4-8 weeks suggests aggregate anaphylaxis as described by A
71-year-old
man
aortic aneurysm.
*Serum immunoglobulins (IgG, IgM, IgA) binding to HES-coated ELISA plates. Serum collected before and after HES administration was preincubated (overnight at 4°C) with various concentrations of HES (0-800 ug per mL serum) and subsequently tested in HESspecific ELISA.
Table: Titres of HES-reactive antibodies in serum the day before and immediately after the adverse reaction, and during
follow-up 49
al.3
This finding also explains why the macrohaemodynamics stabilised on infusion of a further 1 L of HES 10% in our patient. Richter
et
*Uwe Kreimeier, Frank Christ, Dietrich Kraft, Lutz Lauterjung, Markus Niklas, Klaus Peter, Konrad Messmer Departments of *Anaesthesiology and General Surgery, and Institute for Surgical Research, Ludwig-Maximilians-University Munich, Klinikum Grosshadern, D-81377 Munich, Germany; and Institute of General and Experimental Pathology, University of Vienna, Austria 1 2
3
Renck H, Hedin H, Richter W, Wiholm BE. Hapten inhibition and dextran anaphylaxis. Anaesthesia 1988; 43:729-32. Kraft D, Sirtl C, Laubenthal H, et al. No evidence for the existence of preformed antibodies against hydroxyethyl starch in man. Eur Surg Res 1992; 24: 138-42. Richter AW, Hedin HI. Dextran hypersensitivity. Immunol Today 1982; 3: 132-38.
Ljungström KG,
Chronic progressive mumps virus in a child
encephalitis
SiR-The mumps virus can cause acute aseptic meningitis and encephalitis. Some patients with the clinical sequelae of acute mumps virus encephalomeningitis exhibit persistent cerebrospinal fluid (CSF) levels of mumps antibody. 1,2 Except for one reported case,’ these symptoms are selflimiting without progressive deterioration. We have followed a patient with chronic progressive mumps virus encephalitis for 7 years, who had no history of acute mumps virus encephalomeningitis and showed severe progressive psychomotor deterioration and intractable seizures. The patient’s antibodies to the mumps virus were persistently raised in both serum and CSF. However, haemagglutination inhibition (HI) titres were not increased. These findings suggest a new type of chronic encephalitis with onset in childhood similar to subacute sclerosing panencephalitis
(SSPE). This 14-year-old Japanese girl developed normally in early childhood. She had no history of acute mumps virus infection. At the age of 7i years, she exhibited a gradual loss of short-term memory and her school performance got She developed seizures within 2 months. She was first admitted to our hospital at the age of 8 years. Examination showed intellectual deterioration and personality changes. She exhibited emotional lability and aggression, and had daily seizures. An electroencephalogram (EEG) showed a diffuse spike-wave complex that was dominant over the bilateral frontal regions. Magnetic resonance imaging and positron emission tomography scans of the brain were normal. Routine analysis of CSF showed no abnormalities. However, the CSF showed positive oligoclonal IgG bands and an increased IgG index of 8-1 (normal <0-6). Because of suspected chronic viral encephalitis, titres of various viruses were evaluated in the CSF and serum. The patient’s serum was positive for mumps virus antibodies (complement fixation [CF] 1064, HI <8, neutralising test [NT] 32, fluorescent antibody [FA]-IgG 1280, FA-IgM <10, enzyme immunoassay [EIA]-IgG >720896) as was her CSF (CF 64, HI <8, NT 16, FA-IgG 160, FA-IgM <10, EIA-IgG An indirect fluorescent antibody technique using 11264). the patient’s CSF showed positive fluorescence within the inclusion bodies in Vero cells infected by mumps virus. Her CSF showed no positivity for the other viruses tested. Cultures of CSF, blood, urine, and throat swabs were all negative for viruses. Immunological studies showed a relatively low IgG subclass 2 (1-27 mg/mL; normal 0-68-9-51 mg/mL) and a low IgA (0-11 mg/mL). Although the patient was treated with anticonvulsants and inosine pranobex, her intellectual deterioration and motor disability progressed and the frequent seizures persisted. She became worse.
50
bed-ridden at 11 years of age; by 12 years she had severe dementia and did not respond to her surroundings. We again examine her at the age of 12. Magnetic resonance imaging then showed diffuse cortical atrophy that predominated in the frontal lobes. Positron emission tomography revealed glucose hypometabolism in the frontal and temporal cortices. Again, except for HI titres, titres for mumps virus were raised in the CSF and serum to the same extent as in the previous study (CF >2048, HI <8, EIA IgG <41 in HI EIA CF <8, EIA IgG 720896, serum; 32, IgM EIA <41 in 11264, CSF). IgM Vahrei et al’ described a patient with the chronic sequelae of mumps virus encephalitis who showed positivity for mumps antibodies in the CSF, as demonstrated by immunoprecipitation to all mumps virus proteins. However, our patient consistently showed negative HI titres in both serum and CSF. The first described defect of measles virus involved in SSPE was the apparent lack of membrane-matrix (M) protein expression; a defect in M genes was subsequently identified.3 We believe that our patient may have a defect in the haemagglutinin-neuraminidase protein, a mumps virus envelope glycoprotein, which has led to persistent mumps virus infection of the central nervous system. *Kazuhiro
Haginoya, Koichiro Ike, Kazuie linuma, Tsuneo Yagi, Kimiya Kon, Hiroyuki Yokoyama, Yoshio Numazaki *Department of Pediatrics, Tohoku University School of Medicine, Sendai 980, Japan; and Virus Centre, Sendai National Hospital, Sendai 1
2
3
Vahrei A, Julkunen I, Koskiniemi ML. Chronic encephalomyelitis with specific increase in intrathecal mumps antibodies. Lancet 1982; ii: 685-88. Julkunen I, Koskiniemi M, Lehtiniemi EL, Sainio K, Vahrei A. Chronic mumps virus encephalitis: mumps antibody levels in cerebrospinal fluid. J Neuroimmunol 1985; 8: 67-175. Cattaneo R, Schmid A, Rebmann G, et al. Accumulated measles virus mutations in a case of subacute sclerosing panencephalitis: interrupted matrix protein reading frame and transcription alteration. Virology 1986; 154: 97-107
Age-adjusted incidence of hip fractures SiR-Hip fractures in the elderly are a world-wide epidemic, and the predicted ageing of populations is increasing the health-care systems.’I true increases in the number of treatment requiring requires exact knowledge of patients whether the number of hip fractures is increasing more rapidly than can be accounted for by demographic changes alone. Therefore, we determined the current trends in the number and age-adjusted incidence of hip fractures in Finland in 1970-93 by collecting from the National Hospital Discharge Register all patients who were admitted to Finnish hospitals in 1970-72, 1974-75, 1978-80, 1983-85, 1988-89, and 1991-93 for primary treatment of first hip fracture. Ours is the oldest nation-wide discharge register in the world and its accuracy and coverage have been shown to be very good, especially concerning severe injuries such as hip fractures.2,3 The number of hip fractures in Finland (5 million population) increased steadily during the study period, from 2239 in 1970 to 6330 in 1993. The average increase was 7-9% per year. Across the study period, the age-adjusted incidence (per 100 000 in 50-year-old or older individuals) of hip fractures also showed a steady increase from 1970 to 1993: in women, from 275 to 420, and in men, from 108 to 214 (figure). If this trend continues, there will be about three times more hip fractures in Finland in the year 2030 than there were in 1993. Between the 1930s and the 1980s, increasing incidence rates of hip fractures in women and men were seen in all burden of these fractures However, prediction of the
on
our
ray diffraction methods.5 The molecule is a four-helix bundle formed by two antiparallel helix sets, which together with the
connecting loops and a &bgr;-strand form a spiral so that the final surface is similar to that found in proteins of much lower hydrophobicity. This may explain why the protein is easily released from soybean hull dust, and how it can permeate the mucosal membranes of the respiratory tract to produce asthmatic reactions. Our findings indicate that Gly m I is a valuable model to study the mechanism of the human allergic response. The availability of detailed structural information on HPS, and therefore Gly m I, will facilitate the definition of the B-cell and T-cell epitopes involved in the immune response to this allergen. Such knowledge might lead to more effective treatment for these allergies. This
study was supported by Alergia e Inmunologia Abello SA
*R Gonzalez, J Varela, J Carreira, F Polo *Dipartimento Investigación, Alergia e Inmunologia Abelló SA, 19. 28037 Madrid, Spain; and Centro de Investigaciones Biológicas, CSIC Antó JM, Sunyer J, Rodriguez-Roisin R, Suárez-Cervera M, Vázquez L. The Toxicoepidemiological Committee. Community outbreaks of asthma associated with inhalation of soybean dust. N Engl J Med 1989; 320: 1097-102. 2 González R, Zapatero L, Caravaca F, Carreira J. Identification of soybean proteins responsible for respiratory allergies. Int Arch Allergy Appl Immunol 1991; 95: 53-57. 3 González R, Polo F, Zapatero L, Caravaca F, Carreira J. Purification and characterization of major inhalant allergens from soybean hulls. Clin Exp Allergy 1992; 22: 748-55. 4 Odani S, Koide T, Ono T, Seto Y, Tanaka T. Soybean hydrophobic protein: isolation, partial characterization and the complete primary structure. Eur J Biochem 1987; 162: 485-91. 5 Baud F, Pebay-Peyroula E, Cohen-Addad C, Odani S, Lehmann MS. Crystal structure of hydrophobic protein from soybean; a member of a new cysteine-rich family. J Mol Biol 1993; 231: 877-87. 1
Anaphylaxis due to hydroxyethyl-starchreactive antibodies SiR-Colloids are routinely used for primary resuscitation from hypovolaemia and shock and for perioperative fluid management. Synthetic colloids such as dextran or hydroxyethyl starch (HES) improve microcirculatory blood flow and are less expensive than human albumin. However, adverse reactions such as flush, urticaria, hypotension, shock, and even cardiac arrest have been reported for all plasma substitutes in clinical use. An involvement of specific antibodies directed against the colloid eliciting the adverse reaction has been proven for dextran. The naturally occurring dextran-reactive antibodies predominantly belong to the IgG class. With implementation of the hapten prophylaxis (preinjection of 20 mL dextran 1) the incidence of severe dextran-induced anaphylactic reactions for all infusions given was reduced from 0.022% reported between 1975 and 1979 to 0-001% in the years 1983-85.’ By contrast, the exact mechanisms underlying the adverse reactions observed after HES administration are unknown, since preformed antibodies against HES have not been demonstrated so far, even when the highly sensitive ELISA technique was used.2
underwent surgery for an infrarenal History included leucocytosis with absolute hypereosinophilia, and an area of hypoperfusion in the posterior myocardial wall, suggesting an old non-transmural infarction. Induction of anaesthesia was uneventful, and all haemodynamic indices were stable until cross-clamping of the aorta. After clamping blood pressure decreased and pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP) were low (mean arterial pressure [MAP] from 93 to 63 mm Hg; PCWP 5 mm Hg, CVP 2 mm Hg). Therefore intravenous infusion of hyperosmolar HES 10% (molecular weight 200 000/0-5) plus crystalloid solution was started. Within 2 min (after only 20 mL HES) the heart rate dropped from 90 to 45 beats per min and MAP reached 45 mm Hg; at this point cardiac output was 1-8 LJmin (6-0 L/min before clamping of the aorta). Intravenous dopamine was set to 40 mg/h; however, atropine 0-5 mg and adrenaline 0-5 mg had to be administered to normalise the heart rate and raise perfusion pressure to 90 mm Hg. Because PCWP remained low (2 mm Hg), a further 1 L of iso-osmolar HES 10% was infused together with 1 L of crystalloid solution. Since serum concentrations of potassium and haemoglobin as well as blood gas analysis were normal, acute myocardial failure or reinfarction (as a result of increased afterload by crossclamping of the aorta) was assumed. To stabilise haemodynamic indices a total of 1-5 mg adrenaline, 20 mg dopamine, and 2 L of crystalloids were administered, achieving a PCWP of 7 mm Hg. 5 min after declamping, cardiac output amounted to 10.7 L/min, MAP 70 mm Hg, and PCWP 11 mm Hg. The operation was successfully completed and the patient transferred to the intensive-care unit, where he quickly recovered. Compared with a all preoperative electrocardiogram, postoperative electrocardiograms were unchanged and there were no increases in serum creatinine kinase (CK) or CK-MB. Blood samples obtained from the arterial line 10 min after the event were analysed for the presence of HES-reactive antibodies with ELISA. The results were compared with titres measured in serum sampled the day before operation (table). The decrease of HES-specific immunoglobulin titres reflects consumption of antibodies induced by administration of the antigen-ie, HES. This view is supported by the persistent increase in antibody concentration of all immunoglobulin classes except IgE over the following weeks. To our knowledge, the ELISA used is not influenced by the pre-existing absolute eosinophilia of unknown origin. In our patient for the first time high titres of HES-specific antibodies were detected in serum at the time of reaction. Their concentration sharply decreased after giving 1 L of HES. Reappearance of these immunoglobulins, particularly of the IgG class, was observed during the following weeks (table). The neutralisation of antibody titres upon exposure to HES and reappearance of specific antibodies within 4-8 weeks suggests aggregate anaphylaxis as described by A
71-year-old
man
aortic aneurysm.
*Serum immunoglobulins (IgG, IgM, IgA) binding to HES-coated ELISA plates. Serum collected before and after HES administration was preincubated (overnight at 4°C) with various concentrations of HES (0-800 ug per mL serum) and subsequently tested in HESspecific ELISA.
Table: Titres of HES-reactive antibodies in serum the day before and immediately after the adverse reaction, and during
follow-up 49
al.3
This finding also explains why the macrohaemodynamics stabilised on infusion of a further 1 L of HES 10% in our patient. Richter
et
*Uwe Kreimeier, Frank Christ, Dietrich Kraft, Lutz Lauterjung, Markus Niklas, Klaus Peter, Konrad Messmer Departments of *Anaesthesiology and General Surgery, and Institute for Surgical Research, Ludwig-Maximilians-University Munich, Klinikum Grosshadern, D-81377 Munich, Germany; and Institute of General and Experimental Pathology, University of Vienna, Austria 1 2
3
Renck H, Hedin H, Richter W, Wiholm BE. Hapten inhibition and dextran anaphylaxis. Anaesthesia 1988; 43:729-32. Kraft D, Sirtl C, Laubenthal H, et al. No evidence for the existence of preformed antibodies against hydroxyethyl starch in man. Eur Surg Res 1992; 24: 138-42. Richter AW, Hedin HI. Dextran hypersensitivity. Immunol Today 1982; 3: 132-38.
Ljungström KG,
Chronic progressive mumps virus in a child
encephalitis
SiR-The mumps virus can cause acute aseptic meningitis and encephalitis. Some patients with the clinical sequelae of acute mumps virus encephalomeningitis exhibit persistent cerebrospinal fluid (CSF) levels of mumps antibody. 1,2 Except for one reported case,’ these symptoms are selflimiting without progressive deterioration. We have followed a patient with chronic progressive mumps virus encephalitis for 7 years, who had no history of acute mumps virus encephalomeningitis and showed severe progressive psychomotor deterioration and intractable seizures. The patient’s antibodies to the mumps virus were persistently raised in both serum and CSF. However, haemagglutination inhibition (HI) titres were not increased. These findings suggest a new type of chronic encephalitis with onset in childhood similar to subacute sclerosing panencephalitis
(SSPE). This 14-year-old Japanese girl developed normally in early childhood. She had no history of acute mumps virus infection. At the age of 7i years, she exhibited a gradual loss of short-term memory and her school performance got She developed seizures within 2 months. She was first admitted to our hospital at the age of 8 years. Examination showed intellectual deterioration and personality changes. She exhibited emotional lability and aggression, and had daily seizures. An electroencephalogram (EEG) showed a diffuse spike-wave complex that was dominant over the bilateral frontal regions. Magnetic resonance imaging and positron emission tomography scans of the brain were normal. Routine analysis of CSF showed no abnormalities. However, the CSF showed positive oligoclonal IgG bands and an increased IgG index of 8-1 (normal <0-6). Because of suspected chronic viral encephalitis, titres of various viruses were evaluated in the CSF and serum. The patient’s serum was positive for mumps virus antibodies (complement fixation [CF] 1064, HI <8, neutralising test [NT] 32, fluorescent antibody [FA]-IgG 1280, FA-IgM <10, enzyme immunoassay [EIA]-IgG >720896) as was her CSF (CF 64, HI <8, NT 16, FA-IgG 160, FA-IgM <10, EIA-IgG An indirect fluorescent antibody technique using 11264). the patient’s CSF showed positive fluorescence within the inclusion bodies in Vero cells infected by mumps virus. Her CSF showed no positivity for the other viruses tested. Cultures of CSF, blood, urine, and throat swabs were all negative for viruses. Immunological studies showed a relatively low IgG subclass 2 (1-27 mg/mL; normal 0-68-9-51 mg/mL) and a low IgA (0-11 mg/mL). Although the patient was treated with anticonvulsants and inosine pranobex, her intellectual deterioration and motor disability progressed and the frequent seizures persisted. She became worse.
50
bed-ridden at 11 years of age; by 12 years she had severe dementia and did not respond to her surroundings. We again examine her at the age of 12. Magnetic resonance imaging then showed diffuse cortical atrophy that predominated in the frontal lobes. Positron emission tomography revealed glucose hypometabolism in the frontal and temporal cortices. Again, except for HI titres, titres for mumps virus were raised in the CSF and serum to the same extent as in the previous study (CF >2048, HI <8, EIA IgG <41 in HI EIA CF <8, EIA IgG 720896, serum; 32, IgM EIA <41 in 11264, CSF). IgM Vahrei et al’ described a patient with the chronic sequelae of mumps virus encephalitis who showed positivity for mumps antibodies in the CSF, as demonstrated by immunoprecipitation to all mumps virus proteins. However, our patient consistently showed negative HI titres in both serum and CSF. The first described defect of measles virus involved in SSPE was the apparent lack of membrane-matrix (M) protein expression; a defect in M genes was subsequently identified.3 We believe that our patient may have a defect in the haemagglutinin-neuraminidase protein, a mumps virus envelope glycoprotein, which has led to persistent mumps virus infection of the central nervous system. *Kazuhiro
Haginoya, Koichiro Ike, Kazuie linuma, Tsuneo Yagi, Kimiya Kon, Hiroyuki Yokoyama, Yoshio Numazaki *Department of Pediatrics, Tohoku University School of Medicine, Sendai 980, Japan; and Virus Centre, Sendai National Hospital, Sendai 1
2
3
Vahrei A, Julkunen I, Koskiniemi ML. Chronic encephalomyelitis with specific increase in intrathecal mumps antibodies. Lancet 1982; ii: 685-88. Julkunen I, Koskiniemi M, Lehtiniemi EL, Sainio K, Vahrei A. Chronic mumps virus encephalitis: mumps antibody levels in cerebrospinal fluid. J Neuroimmunol 1985; 8: 67-175. Cattaneo R, Schmid A, Rebmann G, et al. Accumulated measles virus mutations in a case of subacute sclerosing panencephalitis: interrupted matrix protein reading frame and transcription alteration. Virology 1986; 154: 97-107
Age-adjusted incidence of hip fractures SiR-Hip fractures in the elderly are a world-wide epidemic, and the predicted ageing of populations is increasing the health-care systems.’I true increases in the number of treatment requiring requires exact knowledge of patients whether the number of hip fractures is increasing more rapidly than can be accounted for by demographic changes alone. Therefore, we determined the current trends in the number and age-adjusted incidence of hip fractures in Finland in 1970-93 by collecting from the National Hospital Discharge Register all patients who were admitted to Finnish hospitals in 1970-72, 1974-75, 1978-80, 1983-85, 1988-89, and 1991-93 for primary treatment of first hip fracture. Ours is the oldest nation-wide discharge register in the world and its accuracy and coverage have been shown to be very good, especially concerning severe injuries such as hip fractures.2,3 The number of hip fractures in Finland (5 million population) increased steadily during the study period, from 2239 in 1970 to 6330 in 1993. The average increase was 7-9% per year. Across the study period, the age-adjusted incidence (per 100 000 in 50-year-old or older individuals) of hip fractures also showed a steady increase from 1970 to 1993: in women, from 275 to 420, and in men, from 108 to 214 (figure). If this trend continues, there will be about three times more hip fractures in Finland in the year 2030 than there were in 1993. Between the 1930s and the 1980s, increasing incidence rates of hip fractures in women and men were seen in all burden of these fractures However, prediction of the
on
our