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A CONTROL, DOUBLE-BLIND COMPARISON OF MEPIVACAINE INJECTION VERSUS SALINE INJECTION FOR MYOFASCIAL PAIN
Saturday 8 March I980
A CONTROL, DOUBLE-BLIND COMPARISON OF MEPIVACAINE INJECTION VERSUS SALINE INJECTION FOR MYOFASCIAL PAIN F. A. FROST
B.
JESSEN
J. SIGGAARD-ANDERSEN Department of Physical Medicine and Rehabilitation and the Laboratory of Clinical Physiology of Exercise, University of Copenhagen, Rigshospitalet, Denmark In a double-blind study 28 patients with acute, localised muscle pain received four local injections of mepivacaine 0·5%, and 25 patients with the same type of pain received local injections of an equivalent volume of physiological saline. The group receiving saline tended to have more relief of pain, especially after the first injection. The results thus show that pain relief is not due merely to the local anæs-
Summary
thetic. The study therefore raises questions about the mechanism by which local injections into muscle relieves pain, since there is the possibility that a similar effect might also be achieved by merely inserting a needle into the trigger point. Physiological saline is considered to be a more appropriate fluid for injection therapy than local anæsthetics since it is less likely to produce side-effects. Introduction PAIN from trigger points is common and often so disabling that the need for treatment is urgent. Empirical injection therapy-i.e., the injection of a local anxsthetic with or without a corticosteroid-has become popular.’ The treatment is aimed at focal, tender areas in the muscles; these areas have an altered consistency and are known as trigger points. The condition is also called fibromyositis. There are various theories on the mechanism of action of injection therapy. Some believe that pain relief is brought about by the insertion of the injection needle (e.g., in acupuncture).2-7 Others believe that pain relief is due to the pharmacological activity of the injected substance;l·89but the type of anaesthetic, its concentration, and the volume of the dose injected are claimed to be of no significance. 10 Whatever the mechanism of action, and despite the widespread use of injection therapy, no clinically controlled study of the efficacy of the local anaesthetic has been reported. We have, therefore, compared the efficacy of the two preparations we normally use-namely, mepivacaine 0-5% (’Carbocaine’) and physiological saline. We use physiological saline as a placebo because it carries no risk of systemic side-effects.
Patients and Methods Patients consisted of ambulant patients admitted to Rigshospitalet and referred to the department of physical medicine for treatment of muscle pain. Those receiving corticosteroids or anticoagulants were excluded. Patients included had to have tender, localised changes in the consistency of the muscle (trigger points), these being the points from which the actual pain could be provoked. The patients accepted that treatment consisted of three injections, but did not know that it was part of a clinical trial. The study began with 60 patients, but 7 (2 who had received mepivacaine and 5 who had received physiological saline) dropped out, 2 because of a worsening in their condition and dissatisfaction with the result of treatment, and 5 patients because of their discharge from hospital before completion of treatment.
Of the 53 patients completing the investigation (34 women and 19 men), 28 received mepivacaine and 25 received physiological saline. Slightly more than half the patients were aged over 50 years. The patients were seen four times in slightly less than 2 weeks. The first three consultations took place at intervals of 2-3 days, the fourth a week after the third. At each of the first three examinations the patient was instructed to pay close attention to the duration of any pain relief after the injection. At the second, third, and fourth consultations, the patient’s condition was compared with that recorded in the initial examination. Patients classified their pain into five groups-symptom-free, considerable improvement, moderate improvement, unchanged, worse. Patients also reported on duration of pain relief. At the fourth examination, patients stated whether they had any discomfort from the treatment and whether they would be prepared to undergo injection therapy again for muscle pain. The injection fluids were supplied in 50 ml capped vials from the pharmacy of Rigshospitalet and then randomised and numbered by a person without any association with our department. The volumes of the injection fluid were pre-determined, according to the region involved (neck, 2 ml; shoulder, 3 ml; lumbar region, 5 ml; gluteal region, 10 ml). Patients received treatment only for that region giving rise to most symptoms. The cumulative pain relief ratio was calculated by the decrement method, and standard deviation (SD) by Greenwood’s estimate.
Results
Fig. 1, 2, and 3 show the cumulative pain relief ratio after the first, second, and third injections, respectively, for patients who had received either mepivacaine or physiological saline. After the first injection, significantly had pain relief with saline than more patients (p<0-03) with mepivacaine (80% compared with 52%), and apart from the first 5 h after the injection, there was significantly more pain relief with the physiological saline than with mepivacaine (fig. 1). 8167 ©
.
500
Pain relief time (hours) Fig. I-Pain relief time after the first injection of mepivacaine (27 patients) or physiological saline (25 patients). Time given
as mean
±SD.
Pain relief time (hours) Fig. 3-Pain relief time after the third injection of mepi (28 patients) or physiological saline (25 patients). Time given as mean ±SD. PATIENTS’
After the first injection, the median duration of pain relief was 3 h for physiological saline and 1h for mepivacaine. After the second injection there was no difference in pain relief between the two groups. The median duration of pain relief was 1 h in both cases. After the third injection (fig. 3), significantly more patients (p<0-03) had pain relief with physiological saline than with mepivacaine (76% compared to 57%). The median duration of pain relief after physiological saline was 4y h and that after mepivacaine was 1 h. Apart from the first hour after the third injection, there was no significant difference in the relief of pain between physiological saline and mepivacaine, and after 4 days, 16% and 18%, of the saline and mepivacaine groups, respectively, continue to be pain free (fig. 3). The accompanying table shows the patients’ assessment of change in symptoms one week after the third in-
jection.
improvement during treatment, compared with 74% of the patients treated with mepivacaine. Considerable improvement or freedom from symptoms was reported in 48% and 42% of these patients, respectively. Only 5 patients reported that their condition had worsened during the treatment (4 during treatment with physiological saline and 1 during treatment with mepi-
1
WEEK AFTER
INJECTION
vacaine-the difference
not
being statistically
cant).
patients found that the inject acceptable and did not cause discomf these 42, 22 had had injections with mepivacaine tients (84%) were prepared to undergo injection again for similar symptoms. 42
apy
out
of the 53
was
68% of the patients treated with physiological saline
reported
ASSESSMENT OF SYMPTOMS
Discussion
an
Although pain relief can generally be assum associated with the local anaesthetic effect of the jected, our study shows that the pain relief is mo to be due to reflex muscle relaxation produced b lation of a reflex arc, the afferent path of which the muscle spindles and the free nerve-endings i sue.
The stimulation can be easily explained by irritant effect of the fluid injected, and the more able effect of physiological saline may be du longer duration of irritation, since nerve impu not blocked by saline. A similar result might pe achieved by merely inserting the needle at th pain,4a procedure which could be investigate control conditions. There is much to suggest th tion therapy of myofascial pain is one form of ture.
Requests for reprints should be addressed to F.A.F Department M, Frederiksberg Hospital, DK-2000 Copenhag
Pain retief time (hours) Fig. 2-Pain relief time after the second injection of mepivacaine (28 patients) or physiological saline (25 patients). Time given
as mean
±SD.
REFERENCES
1. Gross D. Therapeutishe lokalanästhesie. Stuttgart: Hippokrates 2. Zohn DA, McMennell J. Musculoskeletal pain. Boston: Little, B 128-29.
501
CORYNEBACTERIUM VAGINALE AND VAGINITIS: A CONTROLLED TRIAL OF TREATMENT
Patients and Methods 30 non-pregnant women, aged 16-44 yr, were studied. All a malodorous vaginal discharge which had a characteristic microscopical appearance on the wet film and on gram-staining; C. vaginale infection was provisionally diagnosed. The following patients were excluded from the study: those who had used antimicrobial or vaginal medication during the preceding month; those with an intrauterine contraceptive device (IUCD); those with mucopurulent cervical discharge; and those with Trichomonas vaginalis infection (excluded by wet-mount microscopy?) or with yeast or Neisseria goMorr/tfBcB infection. Women who had been in contact with men with nonspecific urethritis were also excluded. The cervix was exposed with an unlubricated bivalve vaginal speculum. Undiluted specimens of vaginal discharge were taken with a plastic loop from the posterior and lateral vaginal fornices; these were smeared on a glass slide for gramstaining and mixed with a drop of saline on another slide for wet-mount microscopy. The gram stain characteristically showed large numbers of gram-variable small coccobacilli (with a pepper-and-salt appearance) and "clue" cells epithelial cells stippled with small coccobacilli2,8). The wet film showed large numbers of coccobacilli, often in rafts or clumps floating between epithelial cells, and sometimes clue cells. Polymorphs were not present in significant numbers. The pH of the vaginal secretions on the tip of the vaginal speculum was measured with indicator paper (range 4.0-5-5). After microscopy a drop of 10% potassium hydroxide was added to the wet-mount specimen and the immediate appearance, or nonappearance, of a "fishy" smell was noted (amine test). Undiluted vaginal discharge was collected with a plain swab from the posterior and lateral fornices, plated immediately on Columbia chocolate agar (CCA), and incubated at 37°C overnight in a candle jar. A swab was also inoculated into Stuart’s transport medium and delivered with the incubated CCA plates to the laboratory the next day. At the laboratory the CCA plates were reincubated in 7% CO2 for a further 24 h. The swabs in transport medium were subcultured on CCA for incubation in 7% CO2; on blood agar for aerobic incubation; and for anaerobic incubation they were subcultured on ISOSensitest Agar (ISA) containing 10% lysed blood and 100 t,tg/ml of gentamicin, and on blood agar containing 15 fLg/ml of nalidixic acid. All plates were incubated at 37°C and examined after 48 h; all growths were recorded. Gram-variable catalase-negative coryneform bacilli isolated in pure growth or as the predominating organisms were subcultured on CCA for purity. In this study all such organisms were called C. vaginale. Two strains were sent to the National Collection of Type Cultures and their identity was confirmed. However, there are considerable difficulties in differentiating C. vaginale from C. vaginale-like organisms,9 and thorough taxonomic investigation is required. This will form part of another study.
complained of
MICHAEL J. BALSDON LINDA PEAD
GEORGE E. TAYLOR ROSALIND MASKELL
Department of Genitourinary Medicine and Public Health Laboratory, St. Mary’s Hospital, Portsmouth
study of the diagnosis and treatof Corynebacterium vaginale (Hœmophilus vaginalis) vaginitis in 30 patients, clinical and microscopical findings were compared with laboratory cultures. The study also included a double-blind randomised trial of treatment regimens including placebo therapy. Laboratory cultures of C. vaginale corresponded well with clinical findings, and we suggest that C. vaginale vaginitis can be reliably diagnosed with clinical and microscopical findings. Tetracycline was effective in half the patients treated, whereas all but 1 of the 17 patients eventually treated with metronidazole were cured. The apparent discrepancy between in-vitro sensitivity and in-vitro efficacy of metronidazole in this
Summary
In
a
ment
condition is discussed. Introduction
ABNORMAL vaginal discharge
not
attributable
to uter-
ine infection, Trichomonas
vaginalis, or yeasts is usually described as non-specific vaginitis and is a common disorder in general practice, gynaecology, and genitourinary medicine. Since 19551 there has been increasing evidence,2-4 disputed by some authors, that Corynebacterium vaginale (Hcemophilus vaginalis) is implicated in most cases of non-specific vaginitis; the significance of this organism, however, has generally been ignored in clinical and laboratory practice.6 Most cases of non-specific vaginitis present with a malodorous vaginal discharge, a pH value of over 5, and clearly defined microscopical appearance. It is almost as common as vulvovaginal candidosis and three times more common than trichomoniasis. Non-specific vaginitis is thought to respond to treatment with metronidazole4 but no trial incorporating placebo has been reported. To test the hypothesis that this syndrome can be diagnosed in a clinic where microscopy is available, that it is associated with C. vaginale in the vagina, and responds to metronidazole, we conducted a double-blind randomised controlled trial incorporating laboratory cultures and placebo therapy.
3. Ghia IN, Mao W, Toomey TC, Gregg IM. Pain 1976; 2: 285-99. 4. Lewit K. Pain 1979; 6: 83-90. 5. Melzack R. How acupuncture can block pain. In: Weisenberg M, ed. Pain, clinical and experimental perspectives. St. Louis; Mosby C.V. 1975: 251-57. 6. Melzack R. The puzzle of pain. New York: Basic Books, 1973: 153-90. 7. Travell J, Rinzler SH. Postgrad Med J 1952; 11: 425-34. 8. Barbor R. A treatment for low back pain. In: Proceedings of the 4th international congress of physical medicine, held in Paris, Sept. 1964. Amsterdam: Excerpta Medica, 1965. 9. Hacket GS. Joint ligament relaxation treated by fibro-osseous proliferation. Springfield,Illinois:CharlesC.Thomas, 1956. 10. Kibler M. Das störungsfeld bei Gelenkserkrankugen und inneren Krankheiten. Stuttgart: Hippokrates, 1958.
(vaginal
Sensitivity to tetracycline and metronidazole was tested in vitro with CCA and impregnated discs containing tetracycline 10 µg, and metronidazole 10 fLg, 25 p.g, and 50 µg. Metronidazole-sensitivity plates were incubated under anaerobic conditions, and tetracycline plates in 7% CO2, for 48 h. Treatment was randomised and double blind, each patient receiving a 7-day course of either metronidazole (400 mg twice daily), oxytetracycline (500 mg twice daily), or two placebo tablets twice daily. Patients were asked to return at 10 days and then 4 wk later. All clinical, microscopical, and microbiological studies were repeated at each visit. No laboratory results were shown to the clinician, nor clinical results to the laboratory until the end of the trial. Clinical cure was the absence of both abnormal vaginal discharge and characteristic microscopical appearance described above. All patients in whom the randomised treatment had failed according to clinical and microscopical results were
A CONTROL, DOUBLE-BLIND COMPARISON OF MEPIVACAINE INJECTION VERSUS SALINE INJECTION FOR MYOFASCIAL PAIN F. A. FROST
B.
JESSEN
J. SIGGAARD-ANDERSEN Department of Physical Medicine and Rehabilitation and the Laboratory of Clinical Physiology of Exercise, University of Copenhagen, Rigshospitalet, Denmark In a double-blind study 28 patients with acute, localised muscle pain received four local injections of mepivacaine 0·5%, and 25 patients with the same type of pain received local injections of an equivalent volume of physiological saline. The group receiving saline tended to have more relief of pain, especially after the first injection. The results thus show that pain relief is not due merely to the local anæs-
Summary
thetic. The study therefore raises questions about the mechanism by which local injections into muscle relieves pain, since there is the possibility that a similar effect might also be achieved by merely inserting a needle into the trigger point. Physiological saline is considered to be a more appropriate fluid for injection therapy than local anæsthetics since it is less likely to produce side-effects. Introduction PAIN from trigger points is common and often so disabling that the need for treatment is urgent. Empirical injection therapy-i.e., the injection of a local anxsthetic with or without a corticosteroid-has become popular.’ The treatment is aimed at focal, tender areas in the muscles; these areas have an altered consistency and are known as trigger points. The condition is also called fibromyositis. There are various theories on the mechanism of action of injection therapy. Some believe that pain relief is brought about by the insertion of the injection needle (e.g., in acupuncture).2-7 Others believe that pain relief is due to the pharmacological activity of the injected substance;l·89but the type of anaesthetic, its concentration, and the volume of the dose injected are claimed to be of no significance. 10 Whatever the mechanism of action, and despite the widespread use of injection therapy, no clinically controlled study of the efficacy of the local anaesthetic has been reported. We have, therefore, compared the efficacy of the two preparations we normally use-namely, mepivacaine 0-5% (’Carbocaine’) and physiological saline. We use physiological saline as a placebo because it carries no risk of systemic side-effects.
Patients and Methods Patients consisted of ambulant patients admitted to Rigshospitalet and referred to the department of physical medicine for treatment of muscle pain. Those receiving corticosteroids or anticoagulants were excluded. Patients included had to have tender, localised changes in the consistency of the muscle (trigger points), these being the points from which the actual pain could be provoked. The patients accepted that treatment consisted of three injections, but did not know that it was part of a clinical trial. The study began with 60 patients, but 7 (2 who had received mepivacaine and 5 who had received physiological saline) dropped out, 2 because of a worsening in their condition and dissatisfaction with the result of treatment, and 5 patients because of their discharge from hospital before completion of treatment.
Of the 53 patients completing the investigation (34 women and 19 men), 28 received mepivacaine and 25 received physiological saline. Slightly more than half the patients were aged over 50 years. The patients were seen four times in slightly less than 2 weeks. The first three consultations took place at intervals of 2-3 days, the fourth a week after the third. At each of the first three examinations the patient was instructed to pay close attention to the duration of any pain relief after the injection. At the second, third, and fourth consultations, the patient’s condition was compared with that recorded in the initial examination. Patients classified their pain into five groups-symptom-free, considerable improvement, moderate improvement, unchanged, worse. Patients also reported on duration of pain relief. At the fourth examination, patients stated whether they had any discomfort from the treatment and whether they would be prepared to undergo injection therapy again for muscle pain. The injection fluids were supplied in 50 ml capped vials from the pharmacy of Rigshospitalet and then randomised and numbered by a person without any association with our department. The volumes of the injection fluid were pre-determined, according to the region involved (neck, 2 ml; shoulder, 3 ml; lumbar region, 5 ml; gluteal region, 10 ml). Patients received treatment only for that region giving rise to most symptoms. The cumulative pain relief ratio was calculated by the decrement method, and standard deviation (SD) by Greenwood’s estimate.
Results
Fig. 1, 2, and 3 show the cumulative pain relief ratio after the first, second, and third injections, respectively, for patients who had received either mepivacaine or physiological saline. After the first injection, significantly had pain relief with saline than more patients (p<0-03) with mepivacaine (80% compared with 52%), and apart from the first 5 h after the injection, there was significantly more pain relief with the physiological saline than with mepivacaine (fig. 1). 8167 ©
.
500
Pain relief time (hours) Fig. I-Pain relief time after the first injection of mepivacaine (27 patients) or physiological saline (25 patients). Time given
as mean
±SD.
Pain relief time (hours) Fig. 3-Pain relief time after the third injection of mepi (28 patients) or physiological saline (25 patients). Time given as mean ±SD. PATIENTS’
After the first injection, the median duration of pain relief was 3 h for physiological saline and 1h for mepivacaine. After the second injection there was no difference in pain relief between the two groups. The median duration of pain relief was 1 h in both cases. After the third injection (fig. 3), significantly more patients (p<0-03) had pain relief with physiological saline than with mepivacaine (76% compared to 57%). The median duration of pain relief after physiological saline was 4y h and that after mepivacaine was 1 h. Apart from the first hour after the third injection, there was no significant difference in the relief of pain between physiological saline and mepivacaine, and after 4 days, 16% and 18%, of the saline and mepivacaine groups, respectively, continue to be pain free (fig. 3). The accompanying table shows the patients’ assessment of change in symptoms one week after the third in-
jection.
improvement during treatment, compared with 74% of the patients treated with mepivacaine. Considerable improvement or freedom from symptoms was reported in 48% and 42% of these patients, respectively. Only 5 patients reported that their condition had worsened during the treatment (4 during treatment with physiological saline and 1 during treatment with mepi-
1
WEEK AFTER
INJECTION
vacaine-the difference
not
being statistically
cant).
patients found that the inject acceptable and did not cause discomf these 42, 22 had had injections with mepivacaine tients (84%) were prepared to undergo injection again for similar symptoms. 42
apy
out
of the 53
was
68% of the patients treated with physiological saline
reported
ASSESSMENT OF SYMPTOMS
Discussion
an
Although pain relief can generally be assum associated with the local anaesthetic effect of the jected, our study shows that the pain relief is mo to be due to reflex muscle relaxation produced b lation of a reflex arc, the afferent path of which the muscle spindles and the free nerve-endings i sue.
The stimulation can be easily explained by irritant effect of the fluid injected, and the more able effect of physiological saline may be du longer duration of irritation, since nerve impu not blocked by saline. A similar result might pe achieved by merely inserting the needle at th pain,4a procedure which could be investigate control conditions. There is much to suggest th tion therapy of myofascial pain is one form of ture.
Requests for reprints should be addressed to F.A.F Department M, Frederiksberg Hospital, DK-2000 Copenhag
Pain retief time (hours) Fig. 2-Pain relief time after the second injection of mepivacaine (28 patients) or physiological saline (25 patients). Time given
as mean
±SD.
REFERENCES
1. Gross D. Therapeutishe lokalanästhesie. Stuttgart: Hippokrates 2. Zohn DA, McMennell J. Musculoskeletal pain. Boston: Little, B 128-29.
501
CORYNEBACTERIUM VAGINALE AND VAGINITIS: A CONTROLLED TRIAL OF TREATMENT
Patients and Methods 30 non-pregnant women, aged 16-44 yr, were studied. All a malodorous vaginal discharge which had a characteristic microscopical appearance on the wet film and on gram-staining; C. vaginale infection was provisionally diagnosed. The following patients were excluded from the study: those who had used antimicrobial or vaginal medication during the preceding month; those with an intrauterine contraceptive device (IUCD); those with mucopurulent cervical discharge; and those with Trichomonas vaginalis infection (excluded by wet-mount microscopy?) or with yeast or Neisseria goMorr/tfBcB infection. Women who had been in contact with men with nonspecific urethritis were also excluded. The cervix was exposed with an unlubricated bivalve vaginal speculum. Undiluted specimens of vaginal discharge were taken with a plastic loop from the posterior and lateral vaginal fornices; these were smeared on a glass slide for gramstaining and mixed with a drop of saline on another slide for wet-mount microscopy. The gram stain characteristically showed large numbers of gram-variable small coccobacilli (with a pepper-and-salt appearance) and "clue" cells epithelial cells stippled with small coccobacilli2,8). The wet film showed large numbers of coccobacilli, often in rafts or clumps floating between epithelial cells, and sometimes clue cells. Polymorphs were not present in significant numbers. The pH of the vaginal secretions on the tip of the vaginal speculum was measured with indicator paper (range 4.0-5-5). After microscopy a drop of 10% potassium hydroxide was added to the wet-mount specimen and the immediate appearance, or nonappearance, of a "fishy" smell was noted (amine test). Undiluted vaginal discharge was collected with a plain swab from the posterior and lateral fornices, plated immediately on Columbia chocolate agar (CCA), and incubated at 37°C overnight in a candle jar. A swab was also inoculated into Stuart’s transport medium and delivered with the incubated CCA plates to the laboratory the next day. At the laboratory the CCA plates were reincubated in 7% CO2 for a further 24 h. The swabs in transport medium were subcultured on CCA for incubation in 7% CO2; on blood agar for aerobic incubation; and for anaerobic incubation they were subcultured on ISOSensitest Agar (ISA) containing 10% lysed blood and 100 t,tg/ml of gentamicin, and on blood agar containing 15 fLg/ml of nalidixic acid. All plates were incubated at 37°C and examined after 48 h; all growths were recorded. Gram-variable catalase-negative coryneform bacilli isolated in pure growth or as the predominating organisms were subcultured on CCA for purity. In this study all such organisms were called C. vaginale. Two strains were sent to the National Collection of Type Cultures and their identity was confirmed. However, there are considerable difficulties in differentiating C. vaginale from C. vaginale-like organisms,9 and thorough taxonomic investigation is required. This will form part of another study.
complained of
MICHAEL J. BALSDON LINDA PEAD
GEORGE E. TAYLOR ROSALIND MASKELL
Department of Genitourinary Medicine and Public Health Laboratory, St. Mary’s Hospital, Portsmouth
study of the diagnosis and treatof Corynebacterium vaginale (Hœmophilus vaginalis) vaginitis in 30 patients, clinical and microscopical findings were compared with laboratory cultures. The study also included a double-blind randomised trial of treatment regimens including placebo therapy. Laboratory cultures of C. vaginale corresponded well with clinical findings, and we suggest that C. vaginale vaginitis can be reliably diagnosed with clinical and microscopical findings. Tetracycline was effective in half the patients treated, whereas all but 1 of the 17 patients eventually treated with metronidazole were cured. The apparent discrepancy between in-vitro sensitivity and in-vitro efficacy of metronidazole in this
Summary
In
a
ment
condition is discussed. Introduction
ABNORMAL vaginal discharge
not
attributable
to uter-
ine infection, Trichomonas
vaginalis, or yeasts is usually described as non-specific vaginitis and is a common disorder in general practice, gynaecology, and genitourinary medicine. Since 19551 there has been increasing evidence,2-4 disputed by some authors, that Corynebacterium vaginale (Hcemophilus vaginalis) is implicated in most cases of non-specific vaginitis; the significance of this organism, however, has generally been ignored in clinical and laboratory practice.6 Most cases of non-specific vaginitis present with a malodorous vaginal discharge, a pH value of over 5, and clearly defined microscopical appearance. It is almost as common as vulvovaginal candidosis and three times more common than trichomoniasis. Non-specific vaginitis is thought to respond to treatment with metronidazole4 but no trial incorporating placebo has been reported. To test the hypothesis that this syndrome can be diagnosed in a clinic where microscopy is available, that it is associated with C. vaginale in the vagina, and responds to metronidazole, we conducted a double-blind randomised controlled trial incorporating laboratory cultures and placebo therapy.
3. Ghia IN, Mao W, Toomey TC, Gregg IM. Pain 1976; 2: 285-99. 4. Lewit K. Pain 1979; 6: 83-90. 5. Melzack R. How acupuncture can block pain. In: Weisenberg M, ed. Pain, clinical and experimental perspectives. St. Louis; Mosby C.V. 1975: 251-57. 6. Melzack R. The puzzle of pain. New York: Basic Books, 1973: 153-90. 7. Travell J, Rinzler SH. Postgrad Med J 1952; 11: 425-34. 8. Barbor R. A treatment for low back pain. In: Proceedings of the 4th international congress of physical medicine, held in Paris, Sept. 1964. Amsterdam: Excerpta Medica, 1965. 9. Hacket GS. Joint ligament relaxation treated by fibro-osseous proliferation. Springfield,Illinois:CharlesC.Thomas, 1956. 10. Kibler M. Das störungsfeld bei Gelenkserkrankugen und inneren Krankheiten. Stuttgart: Hippokrates, 1958.
(vaginal
Sensitivity to tetracycline and metronidazole was tested in vitro with CCA and impregnated discs containing tetracycline 10 µg, and metronidazole 10 fLg, 25 p.g, and 50 µg. Metronidazole-sensitivity plates were incubated under anaerobic conditions, and tetracycline plates in 7% CO2, for 48 h. Treatment was randomised and double blind, each patient receiving a 7-day course of either metronidazole (400 mg twice daily), oxytetracycline (500 mg twice daily), or two placebo tablets twice daily. Patients were asked to return at 10 days and then 4 wk later. All clinical, microscopical, and microbiological studies were repeated at each visit. No laboratory results were shown to the clinician, nor clinical results to the laboratory until the end of the trial. Clinical cure was the absence of both abnormal vaginal discharge and characteristic microscopical appearance described above. All patients in whom the randomised treatment had failed according to clinical and microscopical results were