1160
vomiting (15%), endometritis (8%), over 20 mm Hg change in blood-pressure (3%), fever (2%), pyrexia (2%), adnexitis (1%), and diarrhoea (1%). Endometritis and adnexitis readily responded to therapy, while the other side-effects were transient and tolerable. The most important finding in the study was the observation that M.I. did not increase the prematurity-rate. Of the 716 patients who had had M.i., 536 could be reached for follow-up. Of these 536, 271 (41%) became pregnant with a wanted child after M.I. The prematurity-rate among these 217 patients was 11 %, but for the women who were nulligravidas at the time of M.I., the prematurity-rate was only 8% (see table). In another study’ primigravidas without interrupted pregnancy had 9% prematurity-rate. Delivery before M.I. increased the prematurity-rate in subsequent pregnancy to only 12%, while D. and c. before M.I. increased it to 16% (see table. The mortality-rate of the premature newborns in the group with no D. and c. was 13% and in the D. and c. group it was 20%. In primigravid patients, pregnancy termination with M.I. rather than D. and c. protects the structural integrity of the cervix, as reflected by the low (8%) incidence of prematurity during subsequent pregnancies. This information should be given to patients when discussing with them the available methods for the termination of unwanted pregnancy, and the relative comfort of a 10 min surgical procedure should be weighed against the effect of this procedure on the outcome of subsequent pregnancies with a wanted child. of Obstetrics, and Gynæcology,
Department
University of Debrecen, Hungary, and Washington University, St. Louis, MO 63110, U.S.A.
P. MOCSARY A. I. CSAPO
RED-BLOOD-CELL VOLUME AS AN INDEX OF ALCOHOLISM
SiR,—Professor Whitehead and his colleagues (May 6, p. 978) noted a rising mean red-blood-cell volume (M.c.v.) with increasing alcohol intake, but the figures they give are well within the usually accepted normal range. Whitehead et al. do not state which normal range they accept for the M.c.v. One of us (G. S.) has recently reviewed general-practitioner requests for haematological services in our area. In a six-month period fifty-eight practices submitted a total of 9474 specimens for a full blood-count. 1174 (12-4%) were abnormal. A raised M.c.v. (greater than 98 fl, range 99-128) was the most freqnent single abnormality being found in 386 (33%) of the abnormal bloods. Vitamin B12 and folate estimations were done in 88 of these patients; 17 were vitamin-B,2 deficient and 16 were folate deficient. Thus, in 55 patients the finding was unexplained. The peak frequency was in the 44-66 age-group Some were known to be alcoholic, but in the others it reasonable to suspect that the finding of a raised M.c.v. in the presence of normal vitamin B12 and folate levels might be uncovering evidence of unacknowledged alcohol abuse. In many cases the clinical details were vague, and in keeping with the well-known disinclination of alcoholics to admit their problems. We believe that an increased M.c.v., particularly in the 44-66 age-group, should raise the suspicion of alcohol abuse when no other cause is evident. We would emphasise the need to exclude other causes such as vitamin B12 and folate deficiency (even in patients with normal haemoglobins), liver disease other than that associated with alcohol, and the taking of oral contraceptives in younger women, before this measurement, now widely available to general practitioners, is interpreted as an indication of alcoholism. If vitamin B,2 and folate are not estimated many cases of deficiency will be missed.
(43%).
would
seem
Department of Clinical and Laboratory Hæmatology, Western General
Hospital,
Edinburgh EH4 2XU
G. STOCKDILL N. C. ALLAN
OTOTOXICITY OF ERYTHROMYCIN
SIR,-We have seen two cases of severe hearing loss in patients with azotaemia and liver disease given high doses of erythromycin. Auditory dysfunction is a well-known complication of therapy with aminoglycoside antibiotics, but has previously been associated with erythromycin usage in only three
patients. 1,2
74-year-old woman admitted for staging and chemotherapy of mycosis fungoides. She had been taking prednisone for long-standing, stable inflammatory bowel disease. During the previous 6 months she had had two episodes of cellulitis in the leg caused by group G beta-haemolytic streptococci. Therapy with penicillin and cephalothin was complicated by a rash on each occasion. On the day before admission she had pain, redness, and swelling of the right leg, and on admission she had a fever, numerous palpable nodes, bilateral pleural effusion, and a large area of cellulitis on the right leg. Her serum creatinine was 1-9 mg/dl, total bilirubin 0 - mg/dl, and alkaline phosphatase 260 units normal (30-115); two blood A
cultures grew group g beta-hasmolytic streptococci. She was given erythromycin lactobionate 1 g intravenously every 6 h. Fever and inflammation promptly resolved. However, after 2 days she could hear only very loud sounds, and she complained of tinnitus and vertigo. Erythromycin was replaced by lincomycin. On day 4 the tinnitus, vertigo, and hearing deficit had disappeared, and an audiogram showed high-frequency hearing loss consistent with her age. The serum-alkaline-phosphatase continued to be abnormal, indicating biliary disease. A 60-year-old man known to be allergic to penicillin and a heavy consumer of alcohol had been treated, 1 week before admission, for fever and bronchitis with erythromycin, which he took for 1 day. On the day before admission the fever returned and within 24 h was restless and disoriented. In the emergency room he was found to be febrile, agitated, diaphoretic, and disoriented. A few rales were heard over the left lower lung field. Serum-creatinine 2.2 mg/dl; serum-bilirubin 1.4 mg/dl. Cerebrospinal-fluid studies included a glucose of 74 mg/dl, protein 101 mg/dl, red-blood-cell count 30/mm,3 whiteblood-cell count of 120/mm3 (33% lymphocytes, 67% neutrophils), and no growth on culture. Initial intravenous antibiotic therapy consisted of chloramphenicol 1 g every 6 h and erythromycin lactobionate 1 g every 6 h. Other medications included two 20 mg doses of frusemide. By the third hospital day his serum-creatinine had risen to 6.4 mg/dl due to unexplained renal disease. His spinal-fluid cell-count had improved to 56/mm3 (75% lymphocytes, 25% neutrophils). On the fourth day he was afebrile, but his ability to hear spoken words was much diminished. Erythromycin was decreased to 2 g daily, and discontinued 3 days later. Hearing returned to normal over 3-4 days; an audiogram was not done. Both these patients had an acute hearing loss that was reversed within a few days of discontinuation of, or reduction in the dose of, intravenous erythromycin lactobionate. One patient also had frusemide, but the amount given is unlikely to have been ototoxic even in the presence of advanced renal failure. No drug other than erythromycin could be implicated. This problem has been reported in only three other patients.l.2 The salt used or route of administration are unlikely to have been responsible since the patient described by Eckman et al. had oral erythromycin while the others were treated parenterally. However, all five received at least 4 g erythromycin per day. In addition, three had azotxmia and two of these, the two reported here, had liver disease. The other two patients apparently had intact renal and hepatic function, but received 4-2 g erythromycin in 12 h. The predominant route of excretion of the drug is hepatic,3 but a twofold prolongation of its half-life is observed in the presence of advanced renal failure.’ It therefore seems likely that ototoxi1. Mintz, U., Amir, J., Pmkhas, J., deVries, A. J. Am. med. Ass. 1971, 225, 1122. 2. Eckman, M., Johnson, Tl., Tiess, R. New Engl. J. Med. 1975, 292, 649. 3. Griffith, R., Block, H. Med. Clins N. Am. 1970, 54, 1199. 4. Lee, C., Anderson, R., Chen, K. Proc. Soc. exp. Biol. Med. 1955, 88, 584
vomiting (15%), endometritis (8%), over 20 mm Hg change in blood-pressure (3%), fever (2%), pyrexia (2%), adnexitis (1%), and diarrhoea (1%). Endometritis and adnexitis readily responded to therapy, while the other side-effects were transient and tolerable. The most important finding in the study was the observation that M.I. did not increase the prematurity-rate. Of the 716 patients who had had M.i., 536 could be reached for follow-up. Of these 536, 271 (41%) became pregnant with a wanted child after M.I. The prematurity-rate among these 217 patients was 11 %, but for the women who were nulligravidas at the time of M.I., the prematurity-rate was only 8% (see table). In another study’ primigravidas without interrupted pregnancy had 9% prematurity-rate. Delivery before M.I. increased the prematurity-rate in subsequent pregnancy to only 12%, while D. and c. before M.I. increased it to 16% (see table. The mortality-rate of the premature newborns in the group with no D. and c. was 13% and in the D. and c. group it was 20%. In primigravid patients, pregnancy termination with M.I. rather than D. and c. protects the structural integrity of the cervix, as reflected by the low (8%) incidence of prematurity during subsequent pregnancies. This information should be given to patients when discussing with them the available methods for the termination of unwanted pregnancy, and the relative comfort of a 10 min surgical procedure should be weighed against the effect of this procedure on the outcome of subsequent pregnancies with a wanted child. of Obstetrics, and Gynæcology,
Department
University of Debrecen, Hungary, and Washington University, St. Louis, MO 63110, U.S.A.
P. MOCSARY A. I. CSAPO
RED-BLOOD-CELL VOLUME AS AN INDEX OF ALCOHOLISM
SiR,—Professor Whitehead and his colleagues (May 6, p. 978) noted a rising mean red-blood-cell volume (M.c.v.) with increasing alcohol intake, but the figures they give are well within the usually accepted normal range. Whitehead et al. do not state which normal range they accept for the M.c.v. One of us (G. S.) has recently reviewed general-practitioner requests for haematological services in our area. In a six-month period fifty-eight practices submitted a total of 9474 specimens for a full blood-count. 1174 (12-4%) were abnormal. A raised M.c.v. (greater than 98 fl, range 99-128) was the most freqnent single abnormality being found in 386 (33%) of the abnormal bloods. Vitamin B12 and folate estimations were done in 88 of these patients; 17 were vitamin-B,2 deficient and 16 were folate deficient. Thus, in 55 patients the finding was unexplained. The peak frequency was in the 44-66 age-group Some were known to be alcoholic, but in the others it reasonable to suspect that the finding of a raised M.c.v. in the presence of normal vitamin B12 and folate levels might be uncovering evidence of unacknowledged alcohol abuse. In many cases the clinical details were vague, and in keeping with the well-known disinclination of alcoholics to admit their problems. We believe that an increased M.c.v., particularly in the 44-66 age-group, should raise the suspicion of alcohol abuse when no other cause is evident. We would emphasise the need to exclude other causes such as vitamin B12 and folate deficiency (even in patients with normal haemoglobins), liver disease other than that associated with alcohol, and the taking of oral contraceptives in younger women, before this measurement, now widely available to general practitioners, is interpreted as an indication of alcoholism. If vitamin B,2 and folate are not estimated many cases of deficiency will be missed.
(43%).
would
seem
Department of Clinical and Laboratory Hæmatology, Western General
Hospital,
Edinburgh EH4 2XU
G. STOCKDILL N. C. ALLAN
OTOTOXICITY OF ERYTHROMYCIN
SIR,-We have seen two cases of severe hearing loss in patients with azotaemia and liver disease given high doses of erythromycin. Auditory dysfunction is a well-known complication of therapy with aminoglycoside antibiotics, but has previously been associated with erythromycin usage in only three
patients. 1,2
74-year-old woman admitted for staging and chemotherapy of mycosis fungoides. She had been taking prednisone for long-standing, stable inflammatory bowel disease. During the previous 6 months she had had two episodes of cellulitis in the leg caused by group G beta-haemolytic streptococci. Therapy with penicillin and cephalothin was complicated by a rash on each occasion. On the day before admission she had pain, redness, and swelling of the right leg, and on admission she had a fever, numerous palpable nodes, bilateral pleural effusion, and a large area of cellulitis on the right leg. Her serum creatinine was 1-9 mg/dl, total bilirubin 0 - mg/dl, and alkaline phosphatase 260 units normal (30-115); two blood A
cultures grew group g beta-hasmolytic streptococci. She was given erythromycin lactobionate 1 g intravenously every 6 h. Fever and inflammation promptly resolved. However, after 2 days she could hear only very loud sounds, and she complained of tinnitus and vertigo. Erythromycin was replaced by lincomycin. On day 4 the tinnitus, vertigo, and hearing deficit had disappeared, and an audiogram showed high-frequency hearing loss consistent with her age. The serum-alkaline-phosphatase continued to be abnormal, indicating biliary disease. A 60-year-old man known to be allergic to penicillin and a heavy consumer of alcohol had been treated, 1 week before admission, for fever and bronchitis with erythromycin, which he took for 1 day. On the day before admission the fever returned and within 24 h was restless and disoriented. In the emergency room he was found to be febrile, agitated, diaphoretic, and disoriented. A few rales were heard over the left lower lung field. Serum-creatinine 2.2 mg/dl; serum-bilirubin 1.4 mg/dl. Cerebrospinal-fluid studies included a glucose of 74 mg/dl, protein 101 mg/dl, red-blood-cell count 30/mm,3 whiteblood-cell count of 120/mm3 (33% lymphocytes, 67% neutrophils), and no growth on culture. Initial intravenous antibiotic therapy consisted of chloramphenicol 1 g every 6 h and erythromycin lactobionate 1 g every 6 h. Other medications included two 20 mg doses of frusemide. By the third hospital day his serum-creatinine had risen to 6.4 mg/dl due to unexplained renal disease. His spinal-fluid cell-count had improved to 56/mm3 (75% lymphocytes, 25% neutrophils). On the fourth day he was afebrile, but his ability to hear spoken words was much diminished. Erythromycin was decreased to 2 g daily, and discontinued 3 days later. Hearing returned to normal over 3-4 days; an audiogram was not done. Both these patients had an acute hearing loss that was reversed within a few days of discontinuation of, or reduction in the dose of, intravenous erythromycin lactobionate. One patient also had frusemide, but the amount given is unlikely to have been ototoxic even in the presence of advanced renal failure. No drug other than erythromycin could be implicated. This problem has been reported in only three other patients.l.2 The salt used or route of administration are unlikely to have been responsible since the patient described by Eckman et al. had oral erythromycin while the others were treated parenterally. However, all five received at least 4 g erythromycin per day. In addition, three had azotxmia and two of these, the two reported here, had liver disease. The other two patients apparently had intact renal and hepatic function, but received 4-2 g erythromycin in 12 h. The predominant route of excretion of the drug is hepatic,3 but a twofold prolongation of its half-life is observed in the presence of advanced renal failure.’ It therefore seems likely that ototoxi1. Mintz, U., Amir, J., Pmkhas, J., deVries, A. J. Am. med. Ass. 1971, 225, 1122. 2. Eckman, M., Johnson, Tl., Tiess, R. New Engl. J. Med. 1975, 292, 649. 3. Griffith, R., Block, H. Med. Clins N. Am. 1970, 54, 1199. 4. Lee, C., Anderson, R., Chen, K. Proc. Soc. exp. Biol. Med. 1955, 88, 584
