1138
Communications
in brief
Fig. 1. The fingers on admission to the hospital. The distribution swollen joints are apparent. weakly reactive. LE preparation was weakly positive on two occasions and normal once. Globulin immunoelectrophoresis showed a slightly elevated IgM. A blood volume determination showed a deficit of 500 ml. of whole blood. Gradually over the next 2 weeks, the cyanosis and the pain subsided and the joints became more mobile. Several ischemic ulcers developed on the palmar surface of the finger tips but over a period of a few weeks these ultimately healed and 2 years later the hands are asymptomatic and grossly normal. The only treatment consisted of low molecular weight dextran, 500 ml. per day, which was begun 5 days after admission to the hospital and was continued for 4 days, Although evidence that the above episode was caused by the pill is purely circumstantial, it is none the less highly probable. Coincident with the start of her digital pain, the patient suffered two episodes of blurred vision, a recognized complication of oral contraceptives due to retinal vessel thrombosis. She has continued to smoke half a pack of cigarettes a day as was her custom. She is now asymptomatic, noticing no effects from cold, heat, or smoking, but has taken no birth control pills since hospitalization. The case is presented as another manifestation of the thromboembolic complications of contraceptive medication. Erythema or pain of the finger tips, the first manifestation of this complication in this patient, shouId be considered an indication for cessation of contraceptive medications. REFERENCES
1. Inmann, W. H. W., and Vessey, M. P.: Br. Med. -1. 2: 193, 1968. 2. Miller; D. R.: .Ann. Surg. 173: 135, 1971.
of the skin changes and the
Amniotic fluid and maternal and cord serum levels of gentamicin after intra-amniotic instillation in patients with premature rupture of the membranes DONALD W. FREEMAN, M.D. JOHN M. MATSEN, M.D. NEIL I. ARNOLD, M.D. Department of Obstetrics Hennepin County General Departments of Obstetrics and Laboratory Medicine, Minnesota Medical School, Minnesota
and Gynecology, Hospital and the and Gynecology University of Minneapolis,
E L E v E N patients with premature rupture of the membranes of 12 hours’ duration or longer were selected for intra-amniotic gentamicin therapy. Nme were at or near term, and the duration of pregnancy in the other 2 was 26 weeks and 31 weeks, respectively. Membrane rupture was confirmed in each by the usual means. Patients with evident or suspected intrauterine infection were treated with parenteral antibiotics and were excluded from the study. After preparation of the vagina, 25 mg. of gentamicin in 50 ml. of lactated Ringer’s solution were put into the amniotic sac through a catheter introduced transcervicaily. The catheter was left in place. The antibiotic injection was repeated every 12 hours until delivery except that one patient was given three injections at 8 hour intervals. Amniotic fluid and maternal blood specimens were drawn at intervals for deter-
Volume Number
113 8
Communications
3
in brief
1139
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intra-amniotic
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obtained gentami-
The interval between the beginning of treatment and delivery ranged from 2 hours to 9 days, and the number of injections given each patient varied from 1 to 19. Maternal and cord serum and amniotic fluid levels of gentamicin were assayed according to the plate assay method of Bennett and associates.1 The test organism was Sarcina Eutea (American Type Culture Collection No. 9341). Values for specimen determinations were extrapolated using the formula as described.1 Thirty-nine maternal serum specimens showed levels ranging from less than 0.063 to 6 Pg per milliliter (Fig. 1) . None exceeded 0.6 except for value
of 6.0, which
resulted
technique. The cord serum The time of delivery
from
is believed
an error
0
INJECTION
serum gentamicin Ievels injection of 25 mg.
purpose.
single
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12
mination of gentamicin levels, and blood from the cord was obtained at delivery for the same
possibly
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levels are shown in Fig. 2. ranged from 2 to 12 hours
after the last injection. Five readings were less than 0.063 and 4 others were less than 0.6. The
2
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TIME(HRSKROM
Fig. 2. Cord after tin.
intra-amniotic
6
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LAST
serum gentamicin injection
lb
ii
INJECTION
levels obtained
of 25 mg.
gentami-
remaining 2 were 1 and 2 Pg per milliliter, respectively. Twenty-six amniotic fluid levels were determined at various times after injection, and the values obtained are shown in Fig. 3. Because of the remote possibility of harmful effects to the fetus of prolonged exposure to high IocaI concentrations of gentamicin, the following case report is of some interest. A 20-year-old, para l-O-0-1 patient was admitted with premature rupture of the membranes at 31 weeks’ gestation. She was given 9 intraamniotic injections of gentamicin of 25 mg. each over a period of 4% days. She was then delivered of a 1,790 gram infant by assisted breech extraction after spontaneous onset of labor. Two amniotic fluid gentamicin levels were obtained before delivery. One was 34 cg per milliliter 1 hour after an injection, and the other 0.374 after 10 hours. The cord serum level was 0.235 4 hours and 45 minutes after the last injection. The highest maternal level of 5 determinations was 0.5 Fg per milliliter. The infant has developed normally, and physical examination at 4% months of age was unremarkable.
Maternal
and fetal infection
problems
remain
1140
Communications
August 15, 1977 Am. J. Obstet. Gynecol.
in brief
rl “I
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.
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Fig. 3. Amniotic fluid gentamicin levels obtained after intra-amniotic injection of 25 mg. gentamitin. major complications of premature rupture of membranes. Prophylactic antibiotics administered orally or parenterally have been ineffective in preventing infection over extended time periods2p 3 There is inconclusive evidence that maternal morbidity may be somewhat reduced in this way, but perinatal mortality is not affected. It has been argued that delay in delivery following membrane rupture is justifiable if prematurity is present. Others feel that the risks of infection outweigh any hope of gain resulting from delay of delivery regardless of pregnancy duration, and they consequently advocate an aggressive approach with early termination of pregnancy by the induction of labor or by cesarean section if necessary.4F 5 The accomplishment of early delivery before infection supervenes may present difficulty. Induction of labor may be difficult, and the labor prolonged, particularly if the patient is not at term. The prolonged labor itself increases the infection danger. Cesarean section frequently is necessary because induction is unsuccessful, and
it may be indicated in other cases because of unfavorable fetal presentation. The risk of such an operation is increased because of infection possibilities. The infection danger escalates as time between membrane rupture and delivery increases, but the risk begins the moment rupture occurs. There is general agreement that parenteral antibiotics and prompt termination of pregnancy are indicated when amnionitis is diagnosed. The diagnosis may not be promptly made, however, since the symptoms and findings are often minimal. Furthermore, adequate amniotic fluid levels cannot be obtained with parenteral administration in the case of some antibiotics and may be reached only after several hours in the case of others.61 7 Intra-amniotic injection of the antibiotic, however, produces an effective level immediately, and in the case of gentamicin does so without risk of toxicity to mother or fetus since minimal serum levels develop. A safe and effective method of preventing infection after membrane rupture would carry several advantages. Artificial termination of pregnancy would not be necessary. As a consequence, a desirable prolongation of pregnancy could be achieved in some patients, and difficult and prolonged inductions of labor could be avoided. Fewer cesarean sections for “failed” inductions would result. Finally, if sterilization of the amniotic cavity could be achieved or maintained, the hazards of section would be lessened should this procedure become necessary. Gentamicin sulfate is a broad-spectrum aminoglycoside antibiotic which shows bactericidal action against a wide variety of both gramnegative and gram-positive bacteria, including most organisms which have been implicated in chorioamnionitis and in sepsis and pneumonia of the newborn. The drug is potentially ototoxic and to a lesser degree nephrotoxic, but toxic effects are rare when serum levels do not exceed 10 pg per milliliter. It may be the current drug of choice for intra-amniotic therapy should further studies confirm the value of this approach.
REFERENCES 1. Bennett, J. V., Brodie, J. L., Benner, E. J., and Kirby, W. M.: Appl. Microbial. 14: 170, 1966. 2. Charles, D., and MacAulay, M.: Clin. Obstet. Gynecol. 13: 255, 1970. 3. Gunn, G. C., Mishell, D. R., Jr., and Morton, D. G.: AM. J. OBSTET. GYNECOL. 106: 469, 1970.
Volume Xumber
Communications
113 8
Russell, K. P., and Anderson, G. V.: Am. J. GYNECOL. 83: 930, 1962. Webster, A.: Obstet. Gynecol. Survey 24: 485, 1969. Charles, D.: J. Obstet. Gynaecol. Br. Emp. 61: 750, 1954. Bray, R. E., Boe, R. W., and Johnson, W. L.: AM. J. OBSTET. GYNECOL. 96: 938, 1966. OBSTET.
Alcohols ERIC JOSEPH
of human J. SINGH,
cervical
PH.D.,
mucus
A.R.I.C.
R. SWARTWOUT,
M.D.,
F.A.C.O.G. Department University
of Obstetrics
of
and Gynecology, Illinois
Chicago, Chicago,
THE COMPOSITION of alcohols in human cervical mucus has not been reported to date. Recently, mixtures of such components were isolated from human cervical mucus and analyzed by gas chromatography employing polar and nonpolar packing. Samples of cervical mucus were obtained daily from 4 normal women by aspiration of the cervical canal and pooled (cycle days 7 to 28) at -20° C. and several cycles were collected. Lipids were extracted with chloroformmethanol (2: 1, v/v) as described elsewhere.1 Mucus lipids (1.5 to 2.0 mg.) were saponified by refluxing with 8 per cent sodium hydroxide in 95 per cent ethanol at 16 hours and the contents cooled, taken up in ethyl ether, the base removed by washing with small portions of water, and dried at low temperature with a stream of nitrogen. Removal of the solvent left the unsaponifiable mixture (UNS). UNS as a 1 per cent solution in petroleum ether was passed through a column of alumina (Alcoa F-20) washed previously with petroleum ether. Elution was carried out with petroleum ether alone and containing 5 per cent and 10 per cent chloroform, 100 per cent chloroform, and finally absolute methanol, Evaporation of solvents gave Fractions I-V. Hydrocarbons were present in Fractions I, II, and III, the Fraction IV contained oxygenated components, and Fraction V the sterol and alcohols. The alcoholic Fraction V was acetylated with acetic anhydride preparatory to gas chromatography analysis.2 This work was supported dation 6%0108.
by a grant
from
the Ford
Foun-
Table I. Alcohol mucus (Fraction chromatography)
in brief
1141
distribution in human cervical V from alumina
I
Relative amount
Alcohol+
%
8:0 9:o lo:o 1l:O 12:o 13:o 14:Br 14:o 15:Br 15:Br 15:Uns 15:o 16:Br 16:Br 16:Uns 16:0 17:Br 17:Br 17:o 1B:Uns 18:O 19:Br 19:o 20:Br 20:o 21 :Uns 2l:Br 21:o 22:Br 22:o 23 :Br 23 : Uns 23:0 24:Br 24 : Uns 24:0 25:Br 25 : Uns 25:0 26:0 29:o 30:o 31:o 32:0
1.0 1.0 0.5 T 5.8 0.5 1.0 1.4 1.4 1.0 1.0 0.5 0.5 1.4 0.5 0.5 1.0 1.4 2.4 0.5 1.4 1.4 3.4 1.0 5.8 1.0 8.7 9.1 1.4 2.4 0.5 1.0 5.8 1.0 7.2 9.7 1.0 0.5 7.7 2.4 1.4 1.0 1.4 0.5
t 0.1 t 0.1 r 0.1 + 0.0 2 0.2 + 0.1 2 0.1 t 0.1 2 0.1 + 0.1 P 0.1 t 0.0 + 0.0 + 0.1 r 0.1 t 0.1 + 0.1 c 0.1 t 0.2 + 0.1 t 0.1 t 0.1 t 0.2 + 0.1 + 0.2 2 0.1 t 0.3 f 0.3 + 0.1 t 0.1 t 0.1 t 0.1 t 0.2 + 0.1 t 0.2 + 0.3 -t- 0.1 t 0.1 + 0.2 f 0.1 t 0.1 + 0.1 + 0.1 f 0.1
*Br = branched carbon chain; Uris = unsaturated; T = trace, the component is less than 0.1 per cent. Mean value of four experiments 1 standard deviation.
Samples were subjected to temperature programming in a Barber Colman gas chromatograph Model 5000 with a dual hydrogen flame detector. The rate of heating was 3O C. per minute. The two U-shaped glass columns of 72 x 0.6 inch O.D. was packed with 3 per cent SE-30 on 80 to 100 mesh Gas Chrom P. The injector and detector temperatures were 340 and 350° C., respectively, and column was varied