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Pelvic lymphocyst infection associated with maternally inherited diabetes mellitus
Diabetes Research and Clinical Practice 61 (2003) 137 /141 www.elsevier.com/locate/diabres
Case report
Pelvic lymphocyst infection associated with maternally inherited diabetes mellitus Daisuke Ogawa *, Kenichi Shikata, Mitsuhiro Matsuda, Jun Wada, Haruhito Uchida, Maki Asada, Hirofumi Makino Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan Received 4 April 2002; received in revised form 24 March 2003; accepted 30 April 2003
Abstract A 45-year-old woman with 20-year history of diabetes mellitus was admitted to our hospital because of high fever and abdominal pain. Radical hysterectomy and bilateral pelvic lymphadenectomy had been performed 4 months before admission for invasive cervical cancer. On admission, elastic hard tumors were palpable in the lower abdomen. Laboratory examination showed positive C-reactive protein (CRP), anemia and renal dysfunction. Computed tomography (CT) revealed several lymphocysts in the pelvis. She was diagnosed with infection of pelvic lymphocysts. Since her mother also had diabetes associated with deafness, we examined mitochondrial DNA in leukocytes and detected an A to G transition at the nucleotide position of 3243 (A3243G mutation). She was diagnosed as maternally inherited diabetes mellitus and deafness (MIDD). Puncture of the cysts followed by administration of antibiotics resulted in marked improvement of symptoms and laboratory findings. This is a rare case of pelvic lymphocyst infection in a patient with a mitochondrial disorder. Although the exact mechanism of infection is not clear, MIDD may represent an unusual risk factor for infection, and further investigation is necessary to assess the influence of mitochondrial dysfunction on the immune system. Pelvic lymphocyst infection should be considered in the differential diagnosis of abdominal pain and fever in patients with MIDD after abdominal surgery. # 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Pelvic lymphocysts; Infection; Cervical cancer; Mitochondrial DNA; A3243G mutation
1. Introduction
* Corresponding author. Tel.: /81-86-235-7235; fax: /8186-222-5214. E-mail address: [email protected] (D. Ogawa).
Since mitochondrial dysfunction can affect virtually all organ systems, mitochondrial diseases show a variety of systemic manifestations. Mutations in mitochondrial DNA (mtDNA), including a point mutation of mtDNA at the nucleotide position of 3243, are known to cause diabetes mellitus and deafness. The latter has been identi-
0168-8227/03/$ - see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0168-8227(03)00120-7
138
D. Ogawa et al. / Diabetes Research and Clinical Practice 61 (2003) 137 /141
fied in a pedigree with maternally inherited diabetes mellitus and deafness (MIDD) [1 /3]. It is well known that patients with diabetes mellitus are at risk of developing infectious diseases. However, no previous association between MIDD and opportunistic infections has been reported. Lymphocysts could develop spontaneously after abdominal operation such as radical hysterectomy, however, they usually exist without symptoms and could disappear spontaneously. In this report, we present a case of MIDD with pelvic infection of lymphocysts.
2. Case report A 45-year-old woman was admitted to our hospital on 25 June 1999, due to high fever and lower abdominal pain. The patient had been diagnosed with diabetes mellitus and manifested bilateral hearing loss at 22 years of age. She was treated with insulin but diabetes was poorly controlled. The mother had diabetes mellitus and hearing loss, and her sister and nephew also had diabetes mellitus. The patient had been admitted to another hospital on February 1999, because of International Federation of Gynecology and Obstetrics (FIGO) stage Ib invasive cervical cancer. She underwent radical hysterectomy and pelvic lymphadenectomy. She was admitted to our hospital on 7 May of the same year, because of high fever and abdominal pain and was later diagnosed with infection of pelvic lymphocysts and treated with antibiotics. During the admission, the diagnosis was modified to MIDD based on the presence of deafness and maternally-inherited diabetes mellitus with A3243G mutation of mtDNA. Since glycemic control was poor (HbA1c 8.2%), intensive insulin therapy was started. The patient was later discharged after improvement of clinical symptoms and laboratory findings. However, high fever and lower abdominal pain occurred again, and the patient was referred to our hospital on 22 June for further evaluation and treatment. On admission, body height was 153 cm, body weight 45 kg and body mass index was 19.2 kg/m2.
Body temperature was 38.8 8C, blood pressure was 142/80 mmHg and pulse rate was 112 per min. She reported no diarrhea, polyuria or burning micturition. Abdominal examination revealed elastic hard tumors palpable in the lower abdomen. Neurological and psychiatric examinations indicated mental retardation. There was no evidence of muscular atrophy in all four limbs. Vibration sensation was reduced on bilateral medial malleoli. Deep tendon reflexes were diminished bilaterally. Ophthalmological examination showed simple diabetic retinopathy and audiometric studies showed complete sensorineural hearing loss in both ears. Laboratory data on admission showed white blood cell count of 16.7 /103 per mm3, hemoglobin 9.3 g/dl, platelet count 194 /103 per mm3, aspartate aminotransferase (AST) 8 IU/l, lactic dehydrogenase (LDH) 307 IU/l, creatinine 2.35 mg/dl, HbA1c 6.4% and C-reactive protein (CRP) 9.2 mg/dl. Creatinine clearance was 20.0 ml/min. Urinary protein excretion was 5.27 g/day. Lactic acid was 7.8 mg/dl (normal range: B/10 mg/dl). High resolution computed tomography (CT) of the abdomen (Fig. 1) and ultrasonography (US) of the abdomen showed many lymphocysts with wall thickening. No abnormal findings were found on the electrocardiogram, chest X-ray, and echocardiogram. CT of the brain revealed mild cerebral atrophy and calcification in the basal ganglia. Motor nerve conduction velocity in the median nerve was reduced (24.5 m/s). A diagnosis of pelvic lymphocyst infection was made based on the clinical course and abdominal CT and US findings. Bacterial examinations of blood and urine were negative. Administration of antibiotics, flomoxef 1 g/day, was started, but it was not effective. Puncture of the cysts was performed together with replacement of flomoxef with imipenem cilastatin (1 g/day). Microbiological examination did not demonstrate the presence of any microorganism in the cyst fluid. The treatment resulted in marked improvement of symptoms and clinical findings including a decrease in CRP and resolution of the cysts on abdominal US within 3 weeks. In July 1999, the abdominal pain had completely disappeared and CRP became negative. During the admission, diabetes was controlled well with
D. Ogawa et al. / Diabetes Research and Clinical Practice 61 (2003) 137 /141
139
Fig. 1. Abdominal computed tomography (CT) on admission. Note the presence of several lymphocysts with wall thickening.
intensive insulin therapy. The patient was discharged on 22 July 1999.
3. Discussion Mitochondrial mutation results in a severe disruption of oxidative mitochondrial function, which affects cellular functions throughout the body, and tends to affect most severely those cells with high oxygen consumption such as neurons, myocytes, and endocrine cells. Accordingly, systemic manifestations of mitochondrial diseases vary widely and include encephalopathy, myopathy, and diabetes mellitus. In our patient, the diagnosis of MIDD was based on the presence of diabetes mellitus, deafness and A3243G mutation, although she did not have apparent cardiomyopathy. The possible underlying mechanism is heteroplasmy, which is found in mitochondrial disorders. The mutation is expected to be equally distributed in cells throughout the body in genetic disorders affecting the nuclear DNA. On the other hand, heteroplasmy ensures random distribution of the abnormal mitochondria and the numbers of mitochondria affected may vary dramatically in
different cells and tissues in mitochondrial DNA mutations. The hematopoietic system is also affected by DNA mutation. Pearson’s syndrome, a disorder of the hematopoietic system, occurs in association with single deletions of mtDNA, and it is characterized by sideroblastic anemia with pancytopenia and exocrine pancreatic insufficiency [4]. Recently, several reports have indicated that mitochondrial function correlates with the severity of infection. For example, Adrie et al. [5] demonstrated that the severity of sepsis correlated with mitochondrial membrane potential in circulating monocytes of patients with septicemia, and suggested that mitochondrial membrane potential could be a marker of severity of sepsis. Brealey et al. [6] also demonstrated a relationship between the severity of septicemia and mitochondrial dysfunction in patients with sepsis and multiple organ failure. However, there is no direct evidence that patients with mitochondrial diseases are at high risk of infection. Lacbawan et al. [7] reported a patient with mitochondrial disorder who presented with macrocytic anemia, encephalopathy, and recurrent infection. They postulated that these features were indicative of mtDNA disorder. Although the exact
140
D. Ogawa et al. / Diabetes Research and Clinical Practice 61 (2003) 137 /141
mechanism was not fully elucidated in that study, we speculate that dysfunction of respiratory chain enzymes of the inner mitochondrial membrane could result in both accumulation of toxic free radicals and insufficient energy production for cellular needs. Radical hysterectomy and lymphadenectomy is a standard therapy for cervical cancer. Major complications include bladder dysfunction, urinary infection, wound infection and lymphocyst formation. While the overall complications seem high, the frequency of serious morbidity is low [8]. Lymphocyst formation is a well-known complication after radical hysterectomy with an incidence varying from 2 to 20% [8 /12]. The majority causes no symptoms and usually disappears spontaneously [13]. Most lymphocysts occur within 1 year after surgery and should be differentiated from hematomas and urinomas [13], but they usually resolve spontaneously and produce no major complications [12]. The common pathogens causing lymphocyst infection and the route of infection are still unclear. Infection of lymphocysts rarely occurs and to our knowledge, there is no case report of post-operative infection of abdominal lymphocysts in MIDD patients. An A3243G mutation of mtDNA has been implicated in MIDD [1 /3]. It is well known that infectious diseases occur frequently in patients with diabetes mellitus, and accordingly we speculate that patients with MIDD are susceptible to infectious disease. In fact, Lacbawan et al. [7] suggested previously that mitochondrial dysfunction could be associated with leukocyte dysfunction. In addition, diabetes is sometimes poorly controlled because of mental retardation in MIDD, like this case. Taken together, patients with MIDD might be more susceptible to infection than those with common type diabetes mellitus. Glycemic control in our patient was not extremely poor, but pelvic lymphocyst infection occurred twice. We speculate that such infection was probably due to leukocyte dysfunction associated with mtDNA, although there are no studies of infectious diseases in association with mitochondrial disorders. It is not clear whether infection is a truly rare complication of mitochondrial diabetes or it has been just overlooked as a common
complication of diabetes mellitus. Although further patients need to be examined to reach a definite conclusion, we propose that recognition of cases like ours is clinically important for the proper management of mitochondrial diabetes. In conclusion, this is the first report of pelvic lymphocyst infection associated with MIDD. Lymphocyst infection should be considered in cases of MIDD with high fever and abdominal pain after abdominal operation.
Acknowledgements The authors thank Dr F.G. Issa (http:// www.word-medex.com.au) for the careful reading and editing of the manuscript.
References [1] W. Reardon, R.J. Ross, M.G. Sweeney, L.M. Luxon, M.E. Pembrey, A.E. Harding, et al., Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA, Lancet 340 (1992) 1376 /1379. [2] J.M. van den Ouweland, H.H. Lemkes, R.C. Trembath, R. Ross, G. Velho, D. Cohen, et al., Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene, Diabetes 43 (1994) 746 / 751. [3] T. Kadowaki, H. Kadowaki, Y. Mori, K. Tobe, R. Sakuta, Y. Suzuki, et al., A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA, New Engl. J. Med. 330 (1994) 962 /968. [4] D.R. Johns, Seminars in medicine of the Beth Israel hospital, Boston. Mitochondrial DNA and disease, New Engl. J. Med. 333 (1995) 638 /644. [5] C. Adrie, M. Bachelet, M. Vayssier-Taussat, F. RussoMarie, I. Bouchaert, M. Adib-Conquy, et al., Mitochondrial membrane potential and apoptosis peripheral blood monocytes in severe human sepsis, Am. J. Respir. Crit. Care Med. 164 (2001) 389 /395. [6] D. Brealey, M. Brand, I. Hargreaves, S. Heales, J. Land, R. Smolenski, et al., Association between mitochondrial dysfunction and severity and outcome of septic shock, Lancet 360 (2002) 219 /223. [7] F. Lacbawan, C.J. Tifft, N.L. Luban, S.M. Schmandt, M. Guerrera, S. Weinstein, et al., Clinical heterogeneity in mitochondrial DNA deletion disorders: a diagnostic challenge of Pearson syndrome, Am. J. Med. Genet. 95 (2000) 266 /268.
D. Ogawa et al. / Diabetes Research and Clinical Practice 61 (2003) 137 /141 [8] A. Ayhan, Z.S. Tuncer, H. Yarali, Complications of radical hysterectomy in women with early stage cervical cancer: clinical analysis of 270 cases, Eur. J. Surg. Oncol. 17 (1991) 492 /494. [9] G. Massi, T. Susini, G. Amunni, Extraperitoneal pelvic lymphadenectomy to complement vaginal operations for cervical and endometrial cancer, Int. J. Gynaecol. Obstet. 69 (2000) 27 /35. [10] J.W. Orr, Jr, J.L. Holimon, P.F. Orr, Stage I corpus cancer: is teletherapy necessary, Am. J. Obstet. Gynecol. 176 (1997) 777 /788.
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[11] J.Y. Lin, B. DuBeshter, C. Angel, P.M. Dvoretsky, Morbidity and recurrence with modifications of radical vulvectomy and groin dissection, Gynecol. Oncol. 47 (1992) 80 /86. [12] A. Ilancheran, J.M. Monaghan, Pelvic lymphocyst */a 10-year experience, Gynecol. Oncol. 29 (1988) 333 / 336. [13] Y.M. Fung, W.S. Wong, Malignant lymphocyst after Wertheim’s operation, Gynecol. Oncol. 44 (1992) 288 / 290.
Case report
Pelvic lymphocyst infection associated with maternally inherited diabetes mellitus Daisuke Ogawa *, Kenichi Shikata, Mitsuhiro Matsuda, Jun Wada, Haruhito Uchida, Maki Asada, Hirofumi Makino Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan Received 4 April 2002; received in revised form 24 March 2003; accepted 30 April 2003
Abstract A 45-year-old woman with 20-year history of diabetes mellitus was admitted to our hospital because of high fever and abdominal pain. Radical hysterectomy and bilateral pelvic lymphadenectomy had been performed 4 months before admission for invasive cervical cancer. On admission, elastic hard tumors were palpable in the lower abdomen. Laboratory examination showed positive C-reactive protein (CRP), anemia and renal dysfunction. Computed tomography (CT) revealed several lymphocysts in the pelvis. She was diagnosed with infection of pelvic lymphocysts. Since her mother also had diabetes associated with deafness, we examined mitochondrial DNA in leukocytes and detected an A to G transition at the nucleotide position of 3243 (A3243G mutation). She was diagnosed as maternally inherited diabetes mellitus and deafness (MIDD). Puncture of the cysts followed by administration of antibiotics resulted in marked improvement of symptoms and laboratory findings. This is a rare case of pelvic lymphocyst infection in a patient with a mitochondrial disorder. Although the exact mechanism of infection is not clear, MIDD may represent an unusual risk factor for infection, and further investigation is necessary to assess the influence of mitochondrial dysfunction on the immune system. Pelvic lymphocyst infection should be considered in the differential diagnosis of abdominal pain and fever in patients with MIDD after abdominal surgery. # 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Pelvic lymphocysts; Infection; Cervical cancer; Mitochondrial DNA; A3243G mutation
1. Introduction
* Corresponding author. Tel.: /81-86-235-7235; fax: /8186-222-5214. E-mail address: [email protected] (D. Ogawa).
Since mitochondrial dysfunction can affect virtually all organ systems, mitochondrial diseases show a variety of systemic manifestations. Mutations in mitochondrial DNA (mtDNA), including a point mutation of mtDNA at the nucleotide position of 3243, are known to cause diabetes mellitus and deafness. The latter has been identi-
0168-8227/03/$ - see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0168-8227(03)00120-7
138
D. Ogawa et al. / Diabetes Research and Clinical Practice 61 (2003) 137 /141
fied in a pedigree with maternally inherited diabetes mellitus and deafness (MIDD) [1 /3]. It is well known that patients with diabetes mellitus are at risk of developing infectious diseases. However, no previous association between MIDD and opportunistic infections has been reported. Lymphocysts could develop spontaneously after abdominal operation such as radical hysterectomy, however, they usually exist without symptoms and could disappear spontaneously. In this report, we present a case of MIDD with pelvic infection of lymphocysts.
2. Case report A 45-year-old woman was admitted to our hospital on 25 June 1999, due to high fever and lower abdominal pain. The patient had been diagnosed with diabetes mellitus and manifested bilateral hearing loss at 22 years of age. She was treated with insulin but diabetes was poorly controlled. The mother had diabetes mellitus and hearing loss, and her sister and nephew also had diabetes mellitus. The patient had been admitted to another hospital on February 1999, because of International Federation of Gynecology and Obstetrics (FIGO) stage Ib invasive cervical cancer. She underwent radical hysterectomy and pelvic lymphadenectomy. She was admitted to our hospital on 7 May of the same year, because of high fever and abdominal pain and was later diagnosed with infection of pelvic lymphocysts and treated with antibiotics. During the admission, the diagnosis was modified to MIDD based on the presence of deafness and maternally-inherited diabetes mellitus with A3243G mutation of mtDNA. Since glycemic control was poor (HbA1c 8.2%), intensive insulin therapy was started. The patient was later discharged after improvement of clinical symptoms and laboratory findings. However, high fever and lower abdominal pain occurred again, and the patient was referred to our hospital on 22 June for further evaluation and treatment. On admission, body height was 153 cm, body weight 45 kg and body mass index was 19.2 kg/m2.
Body temperature was 38.8 8C, blood pressure was 142/80 mmHg and pulse rate was 112 per min. She reported no diarrhea, polyuria or burning micturition. Abdominal examination revealed elastic hard tumors palpable in the lower abdomen. Neurological and psychiatric examinations indicated mental retardation. There was no evidence of muscular atrophy in all four limbs. Vibration sensation was reduced on bilateral medial malleoli. Deep tendon reflexes were diminished bilaterally. Ophthalmological examination showed simple diabetic retinopathy and audiometric studies showed complete sensorineural hearing loss in both ears. Laboratory data on admission showed white blood cell count of 16.7 /103 per mm3, hemoglobin 9.3 g/dl, platelet count 194 /103 per mm3, aspartate aminotransferase (AST) 8 IU/l, lactic dehydrogenase (LDH) 307 IU/l, creatinine 2.35 mg/dl, HbA1c 6.4% and C-reactive protein (CRP) 9.2 mg/dl. Creatinine clearance was 20.0 ml/min. Urinary protein excretion was 5.27 g/day. Lactic acid was 7.8 mg/dl (normal range: B/10 mg/dl). High resolution computed tomography (CT) of the abdomen (Fig. 1) and ultrasonography (US) of the abdomen showed many lymphocysts with wall thickening. No abnormal findings were found on the electrocardiogram, chest X-ray, and echocardiogram. CT of the brain revealed mild cerebral atrophy and calcification in the basal ganglia. Motor nerve conduction velocity in the median nerve was reduced (24.5 m/s). A diagnosis of pelvic lymphocyst infection was made based on the clinical course and abdominal CT and US findings. Bacterial examinations of blood and urine were negative. Administration of antibiotics, flomoxef 1 g/day, was started, but it was not effective. Puncture of the cysts was performed together with replacement of flomoxef with imipenem cilastatin (1 g/day). Microbiological examination did not demonstrate the presence of any microorganism in the cyst fluid. The treatment resulted in marked improvement of symptoms and clinical findings including a decrease in CRP and resolution of the cysts on abdominal US within 3 weeks. In July 1999, the abdominal pain had completely disappeared and CRP became negative. During the admission, diabetes was controlled well with
D. Ogawa et al. / Diabetes Research and Clinical Practice 61 (2003) 137 /141
139
Fig. 1. Abdominal computed tomography (CT) on admission. Note the presence of several lymphocysts with wall thickening.
intensive insulin therapy. The patient was discharged on 22 July 1999.
3. Discussion Mitochondrial mutation results in a severe disruption of oxidative mitochondrial function, which affects cellular functions throughout the body, and tends to affect most severely those cells with high oxygen consumption such as neurons, myocytes, and endocrine cells. Accordingly, systemic manifestations of mitochondrial diseases vary widely and include encephalopathy, myopathy, and diabetes mellitus. In our patient, the diagnosis of MIDD was based on the presence of diabetes mellitus, deafness and A3243G mutation, although she did not have apparent cardiomyopathy. The possible underlying mechanism is heteroplasmy, which is found in mitochondrial disorders. The mutation is expected to be equally distributed in cells throughout the body in genetic disorders affecting the nuclear DNA. On the other hand, heteroplasmy ensures random distribution of the abnormal mitochondria and the numbers of mitochondria affected may vary dramatically in
different cells and tissues in mitochondrial DNA mutations. The hematopoietic system is also affected by DNA mutation. Pearson’s syndrome, a disorder of the hematopoietic system, occurs in association with single deletions of mtDNA, and it is characterized by sideroblastic anemia with pancytopenia and exocrine pancreatic insufficiency [4]. Recently, several reports have indicated that mitochondrial function correlates with the severity of infection. For example, Adrie et al. [5] demonstrated that the severity of sepsis correlated with mitochondrial membrane potential in circulating monocytes of patients with septicemia, and suggested that mitochondrial membrane potential could be a marker of severity of sepsis. Brealey et al. [6] also demonstrated a relationship between the severity of septicemia and mitochondrial dysfunction in patients with sepsis and multiple organ failure. However, there is no direct evidence that patients with mitochondrial diseases are at high risk of infection. Lacbawan et al. [7] reported a patient with mitochondrial disorder who presented with macrocytic anemia, encephalopathy, and recurrent infection. They postulated that these features were indicative of mtDNA disorder. Although the exact
140
D. Ogawa et al. / Diabetes Research and Clinical Practice 61 (2003) 137 /141
mechanism was not fully elucidated in that study, we speculate that dysfunction of respiratory chain enzymes of the inner mitochondrial membrane could result in both accumulation of toxic free radicals and insufficient energy production for cellular needs. Radical hysterectomy and lymphadenectomy is a standard therapy for cervical cancer. Major complications include bladder dysfunction, urinary infection, wound infection and lymphocyst formation. While the overall complications seem high, the frequency of serious morbidity is low [8]. Lymphocyst formation is a well-known complication after radical hysterectomy with an incidence varying from 2 to 20% [8 /12]. The majority causes no symptoms and usually disappears spontaneously [13]. Most lymphocysts occur within 1 year after surgery and should be differentiated from hematomas and urinomas [13], but they usually resolve spontaneously and produce no major complications [12]. The common pathogens causing lymphocyst infection and the route of infection are still unclear. Infection of lymphocysts rarely occurs and to our knowledge, there is no case report of post-operative infection of abdominal lymphocysts in MIDD patients. An A3243G mutation of mtDNA has been implicated in MIDD [1 /3]. It is well known that infectious diseases occur frequently in patients with diabetes mellitus, and accordingly we speculate that patients with MIDD are susceptible to infectious disease. In fact, Lacbawan et al. [7] suggested previously that mitochondrial dysfunction could be associated with leukocyte dysfunction. In addition, diabetes is sometimes poorly controlled because of mental retardation in MIDD, like this case. Taken together, patients with MIDD might be more susceptible to infection than those with common type diabetes mellitus. Glycemic control in our patient was not extremely poor, but pelvic lymphocyst infection occurred twice. We speculate that such infection was probably due to leukocyte dysfunction associated with mtDNA, although there are no studies of infectious diseases in association with mitochondrial disorders. It is not clear whether infection is a truly rare complication of mitochondrial diabetes or it has been just overlooked as a common
complication of diabetes mellitus. Although further patients need to be examined to reach a definite conclusion, we propose that recognition of cases like ours is clinically important for the proper management of mitochondrial diabetes. In conclusion, this is the first report of pelvic lymphocyst infection associated with MIDD. Lymphocyst infection should be considered in cases of MIDD with high fever and abdominal pain after abdominal operation.
Acknowledgements The authors thank Dr F.G. Issa (http:// www.word-medex.com.au) for the careful reading and editing of the manuscript.
References [1] W. Reardon, R.J. Ross, M.G. Sweeney, L.M. Luxon, M.E. Pembrey, A.E. Harding, et al., Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA, Lancet 340 (1992) 1376 /1379. [2] J.M. van den Ouweland, H.H. Lemkes, R.C. Trembath, R. Ross, G. Velho, D. Cohen, et al., Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene, Diabetes 43 (1994) 746 / 751. [3] T. Kadowaki, H. Kadowaki, Y. Mori, K. Tobe, R. Sakuta, Y. Suzuki, et al., A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA, New Engl. J. Med. 330 (1994) 962 /968. [4] D.R. Johns, Seminars in medicine of the Beth Israel hospital, Boston. Mitochondrial DNA and disease, New Engl. J. Med. 333 (1995) 638 /644. [5] C. Adrie, M. Bachelet, M. Vayssier-Taussat, F. RussoMarie, I. Bouchaert, M. Adib-Conquy, et al., Mitochondrial membrane potential and apoptosis peripheral blood monocytes in severe human sepsis, Am. J. Respir. Crit. Care Med. 164 (2001) 389 /395. [6] D. Brealey, M. Brand, I. Hargreaves, S. Heales, J. Land, R. Smolenski, et al., Association between mitochondrial dysfunction and severity and outcome of septic shock, Lancet 360 (2002) 219 /223. [7] F. Lacbawan, C.J. Tifft, N.L. Luban, S.M. Schmandt, M. Guerrera, S. Weinstein, et al., Clinical heterogeneity in mitochondrial DNA deletion disorders: a diagnostic challenge of Pearson syndrome, Am. J. Med. Genet. 95 (2000) 266 /268.
D. Ogawa et al. / Diabetes Research and Clinical Practice 61 (2003) 137 /141 [8] A. Ayhan, Z.S. Tuncer, H. Yarali, Complications of radical hysterectomy in women with early stage cervical cancer: clinical analysis of 270 cases, Eur. J. Surg. Oncol. 17 (1991) 492 /494. [9] G. Massi, T. Susini, G. Amunni, Extraperitoneal pelvic lymphadenectomy to complement vaginal operations for cervical and endometrial cancer, Int. J. Gynaecol. Obstet. 69 (2000) 27 /35. [10] J.W. Orr, Jr, J.L. Holimon, P.F. Orr, Stage I corpus cancer: is teletherapy necessary, Am. J. Obstet. Gynecol. 176 (1997) 777 /788.
141
[11] J.Y. Lin, B. DuBeshter, C. Angel, P.M. Dvoretsky, Morbidity and recurrence with modifications of radical vulvectomy and groin dissection, Gynecol. Oncol. 47 (1992) 80 /86. [12] A. Ilancheran, J.M. Monaghan, Pelvic lymphocyst */a 10-year experience, Gynecol. Oncol. 29 (1988) 333 / 336. [13] Y.M. Fung, W.S. Wong, Malignant lymphocyst after Wertheim’s operation, Gynecol. Oncol. 44 (1992) 288 / 290.