Does surgery improve live birth rates in patients with recurrent miscarriage caused by uterine anomalies?

We found that congenital uterine anomalies have a negative impact on reproductive outcome in recurrent-miscarriage couples, being associated with further miscarriage with a normal embryonic karyotype. There has been no study comparing live birth rates between patients with and without surgery. We conducted a prospective study to prove that surgery for a bicornuate or septate uterus might improve the live birth rate. A total of 170 patients with congenital uterine anomalies suffering two or more miscarriages were examined. The live birth rate after ascertainment of anomalies, cumulative live birth rate and infertility rate, were compared between patients with and without surgery. In patients with a septate uterus, the live birth rate (81.3%) at the first pregnancy after ascertainment of anomalies with surgery tended to be higher than that (61.5%) in those without surgery. The infertility rates were similar in both groups, while the cumulative live birth rate (76.1%) tended to be higher than without surgery (60.0%). Surgery showed no benefit in patients with a bicornuate uterus for having a baby, but tended to decrease the preterm birth rate and the low birth weight. The possibility that surgery has benefits for having a baby in patients with a septate uterus suffering recurrent miscarriage could not be excluded.

Production of human monoclonal anti-basement membrane zone (BMZ) antibodies from a patient with bullous pemphigoid (BP) by Epstein-Barr virus transformation. Analyses of the heterogeneity of anti-BMZ antibodies in BP sera using them.

We established three lymphoblastoid cell lines from a bullous pemphigoid (BP) patient's peripheral blood by means of EBV transformation, which produced human monoclonal anti-basement membrane zone (BMZ) IgG antibodies. A blocking immunofluorescence test using these MAbs, designated 5A, 5E, and 10D, revealed that 5A and 5E recognized the same or a closely associated epitope, but the epitope for 10D was completely different, 18 of 30 BP sera blocked the reactivity of 10D MAb and 17 sera blocked 5E, while 9 sera did not block the staining of either antibody. Immunoblot analysis demonstrated that both 5A and 5E MAbs reacted exclusively with a protein band of approximately 230 kD in normal human epidermal extracts. However, 10D did not show any protein band. 22 of 30 BP sera strongly reacted with the same 230-kD protein, while none of control sera showed such reactivity. These results clearly demonstrated the heterogeneity of anti-BMZ antibodies in terms of epitopes. These MAbs should be useful in future investigations concerning not only the immunopathology but also the biochemial and molecular analyses of the BP antigen.

Factor XII, kininogen and plasma prekallikrein in abnormal pregnancies.

Factor XII, plasma prekallikrein and high molecular weight kininogen were first identified as coagulation proteins in the intrinsic pathway because patients deficient in these proteins had marked prolongation of in vitro surface-activated coagulation time. However, deficiencies of these proteins are not associated with clinical bleeding. Paradoxically, studies suggest that these proteins have anticoagulant and profibrinolytic activities. In fact, association between deficiencies of these proteins and thrombosis has been reported. Also, deficiencies of these proteins, auto-antibodies to these proteins and anti-phospholipid antibodies are frequent hemostatis-related abnormalities found in unexplained recurrent aborters. Recently, evidence has accumulated for the presence of the kallikrein-kininogen-kinin system in the fetoplacental unit. Since contact proteins or kallikrein-kininogen-kinin system may play an important role in pregnancy especially in the fetoplacental unit, deficiencies of these proteins and/or auto-antibodies to these proteins may be associated with pregnancy losses. These possibilities will be reviewed, the functions of the individual components will be summarized, and their role in blood coagulation and pregnancy discussed.

Serum hepatocyte growth factor in patients with peripheral arterial occlusive disease.

Hepatocyte growth factor (HGF) is a multifunctional protein implicated in tissue regeneration, wound healing, and angiogenesis. We measured serum HGF concentrations in 37 patients with peripheral arterial occlusive disease (PAOD). Among them, 36 patients underwent arteriography. Serum HGF concentrations were also measured in 40 control subjects who remained free of vascular, liver, kidney, or lung disease. Patients with PAOD showed elevated serum HGF concentrations compared with control subjects (0.40+/-0.02 vs. 0.19+/-0.01 ng/mL; P<0.001). Serum HGF concentrations were significantly higher in smokers compared with nonsmokers (0.45+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.003). The serum HGF concentrations in patients with collaterals tended to be higher than those in patients without collaterals (0.43+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.06). Moreover, in patients who underwent bypass surgery or angioplasty, serum HGF concentrations decreased from 0.41+/-0.03 to 0.21+/-0.04 ng/mL after treatment (P<0.001). Serum HGF may be an useful marker for the diagnosis of PAOD. HGF may play an important role in angiogenesis and collateral vessel growth in PAOD.

Kininogen domain 3 contains regions recognized by antiphosphatidylethanolamine antibodies.

Antiphosphatidylethanolamine antibodies (APE) have been described in patients with thrombotic diseases and recurrent pregnancy loss (RPL). It has been reported that certain APE are not specific for phosphatidylethanolamine (PE) per se, but are directed to PE-binding plasma proteins, called kininogens. Our recent in vitro data suggest that APE may recognize the domain 3 (D3) region of kininogens. In this study, we have used synthetic peptides that span the D3 of kininogens in inhibition and direct binding studies to identify epitopes that are sites for binding APE. Our present data demonstrate that among 24 RPL patients who were positive for kininogen-dependent immunoglobulin (IgG) APE, 17 patients (70.8%) recognized the LDC27 peptide. We mapped the APE-binding region on D3 using plasma from a RPL patient (X) who had a high titer of IgG APE that recognized LDC27. APE of patient X recognized a 13-residue segment in LDC27, named CNA13. Leu331-Met357 (LDC27) and Cys333-Lys345 (CNA13) are located on the carboxyl-terminal portion of kininogen D3, which is known as the major kininogen heavy chain cell attachment site where it overlaps its cysteine protease inhibitory region. Because APE interferes with the balance of hemostasis in vitro, APE may therefore induce a similar condition in patients thereby causing thrombosis and RPL.

Phosphatidylethanolamine induces specific conformational changes in the kininogens recognizable by antiphosphatidylethanolamine antibodies.

Autoantibodies to the zwitterionic phospholipid (PL), phosphatidylethanolamine (PE) have been described in patients with thrombotic diseases. Recently, we reported that many antiphosphatidylethanolamine antibodies (aPE) are not specific for PE per se, but are directed to plasma proteins which can bind PE, for example, high molecular weight kininogen (HK), low molecular weight kininogen (LK) and/or proteins in complex with HK, factor XI or prekallikrein. In the ELISA, we now show that intact HK binds to all PL tested. By using a monoclonal antibody (mAb) to the HK light chain, binding to cardiolipin (CL) was highest followed by phosphatidylserine (PS), PE and phosphatidylcholine (PC). By contrast, LK bound best to PE, with lesser amounts binding to PC and CL. Many aPE recognize only a kininogen-PE complex and neither PE nor kininogen when they are tested independently. We now report that these aPE are specific for the kininogen-PE complex as they do not recognize the kininogens when the latter are presented on other PL substrates. This indicates that PE induces unique antigenic conformational changes in the kininogens which are not induced when the kininogens bind to other PL. The kininogens bind to platelets and endothelial cells through an as yet undefined receptor. Since PE is a normal constituent of the outer layer of cell and platelet plasma membranes, it is available for the kininogens to bind. In vitro studies showed that purified IgG which bound kininogen-PE complexes in ELISA also caused platelets to undergo irreversible aggregation when stimulated by subthreshold concentrations of bovine thrombin.

Flow-cytometric analysis of immune cell populations in human decidua from various types of first-trimester pregnancy.

We undertook an investigation in which flow cytometry was used to characterize immune cell populations in the decidua of first-trimester normal pregnancies, spontaneous abortions, and ectopic pregnancies in comparison to the nonpregnant endometrium to demonstrate how the proportions of immunocompetent cell populations at the fetomaternal interface are influenced by the presence and state of a fetoplacental allograft. No significant differences were found in the decidua of the different types of first-trimester pregnancy in the proportions of the CD45+, CD14+, CD3+, CD4+, CD8+, CD19+, CD3-/CD16+ and/or CD56+, CD3+/CD16+ and/or CD56+, CD4+/Leu-8+, CD4+/Leu-8-, CD8+/CD11b+, CD8+/CD11b-, and CD3+/HLA-DR- decidual leukocyte subsets. However, the percentage of decidual CD3+/HLA-DR+ cells, which are characteristic of activated T cells, was significantly higher in spontaneous abortions than in normal pregnancies (p less than 0.05). This suggests that the accumulation of decidual leukocytes may be regulated mainly by hormones and/or cytokines rather than by the presence and state of an intrauterine conceptus and that on/off-switching of activation of decidual T cells may be associated with successful maintenance of the implanted embryo.

Plasma contact system, kallikrein-kinin system and antiphospholipid-protein antibodies in thrombosis and pregnancy.

Coagulation factor XII, prekallikrein and high molecular weight kininogen are known as plasma contact proteins in the intrinsic pathway of blood coagulation. Deficiencies of these proteins are not associated with clinical bleeding despite marked prolongation of in vitro surface-activated coagulation time. Paradoxically, studies suggest that these proteins have anticoagulant and profibrinolytic activities. In fact, association between deficiencies of these proteins as well as recurrent thrombosis has been reported. Also deficiencies of these proteins and antiphospholipid antibodies are frequent haemostasis-related abnormalities found in unexplained recurrent aborters. Recently, evidence has accumulated for the presence of the kallikrein-kinin system or plasma contact system in the fetoplacental unit. This suggests that the plasma contact system may also have an important role in pregnancy. Several studies have reported the presence of autoantibodies to the contact proteins in patients with SLE, thrombosis and recurrent pregnancy loss. These autoantibodies are often in association with antiphospholipid antibodies and lupus anticoagulants. Contact proteins may be added to the list of proteins to which autoantibodies are produced in patients assigned to antiphospholipid antibody syndrome.

Current comprehensive therapy of habitual abortion.

Habitual abortion is sometimes an incurable pathogenetic state. Even more serious to both the patient and gynecologist is that the incidence of repeated reproductive wastage is higher in subsequent pregnancies. We registered more than 1,000 women with repeated spontaneous abortions in this clinic for 5 years and analyzed their pathogenesis for the wastages by several different approaches. One hundred twenty-four women were diagnosed as having a congenital uterine abnormality. Metroplasty was performed in 50 patients, resulting in 82% successful subsequent pregnancies, whereas more than 98% of the pregnancies had terminated in spontaneous abortion before the operation. By measuring anticardiolipin antibody (ACA) and lupus anticoagulant (LA), the present study diagnosed several cases as antiphospholipid syndrome, and successfully pregnant patients were observed and treated with appropriate medications. Fifty-five partners of 54 couples had either a chromosomal abnormality or normal variants, showing a high incidence of spontaneous abortion in each type of abnormality. In the other 311 cases, female partners were treated by the immunotherapy of the husbands' lymphocytes in pre- and postgestational periods. Among them, 200 women became pregnant, and 147 cases successfully maintained the pregnancy. These studies indicate that early diagnosis through comprehensive examinations is essential for effective treatment of curable fetal loss in human reproduction.

The effect of mild microembolic injury on the energy metabolism of the cat brain.

Moderate unilateral cerebral ischemia was produced by microembolism in 24 adult cats. Two million plastic microspheres with a diameter of 15 +/- 5 microns were injected into the left common carotid artery via the lingual artery. The physiological and metabolic responses to embolism were accessed by electrocorticography and by determining the cerebral energy state. Embolism caused an immediate slowing and voltage reduction of the ipsilateral electrocorticogram with a gradual recovery after 30 to 60 min. Some animals also had an immediate and short depression of the contralateral electrocorticogram. In spite of the market functional suppression, metabolites of the cerebral energy-producing metabolism in most of the animals changed only slightly. In the embolized hemisphere pyruvate increased from 0.06 to 0.10 mumol/g and lactate from 1.9 to 4.6 mumol/g within 5 min after embolization and remained at this level during the 4 h observation period. Phosphocreatine, adenosine triphosphate and the energy charge of the adenylate pool remained uncharged during this period. However, there was a slight increase of ATP in the non-embolized hemisphere during the early postembolic period. In two animals, the initial slowing of the electrocorticogram recurred and spread to the contralateral hemisphere, followed by bilateral flattening after a few hours. This delayed functional deterioration was accomplished by complete loss of energy-rich phosphates. These animals also had a progressive increase of cerebrospinal fluid (CSF) pressure and considerable brain swelling with cerebellar herniation after 4 h. It is concluded that unilateral cerebral embolism in the above concentration leads only to a slight increase of anerobic glycolysis without significant perturbation of the cerebral energy state, unless progressive brain swelling with cerebrellat herniation supervenes. This supports previous findings, that brain edema and not initial ischemia is the main pathogenetic factor for tissue damage in cerebral microembolism.

Prevalence and heterogeneity of antiphosphatidylethanolamine antibodies in patients with recurrent early pregnancy losses.

OBJECTIVE: To describe the prevalence of antiphospholipid antibodies to both anionic and zwitterionic phospholipids in women with early recurrent pregnancy losses (RPLs). DESIGN: Retrospective data analysis. SETTING: Tokai University Hospital, Kanagawa, Japan. PATIENT(S): One hundred thirty-nine patients with unexplained early RPLs. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Enzyme-linked immunosorbent assays were used to measure autoantibodies to phosphatidylethanolamine, cardiolipin, and phosphatidylserine. RESULT(S): Twenty-eight (20.1%), 17 (12.2%), and 2 (1.4%) patients of the 139 total patients were positive for immunoglobulin (Ig) G, IgM, and IgA antiphosphatidylethanolamine antibodies, respectively. Because 3 patients had two isotypes, 44 (31.7%) of the patients were positive for antiphosphatidylethanolamine antibodies. Six patients (4.3%) and 1 patient (0.7%) were positive for IgG and IgM antiphosphatidylserine antibodies, respectively. Seven patients (5%) were positive for beta2-glycoprotein I-independent anticardiolipin IgG, and 1 patient was positive for beta2-glycoprotein I-dependent anticardiolipin IgG. Two patients (1.4%) had lupus anticoagulant. CONCLUSION(S): Our data show a statistically stronger association between RPLs and antiphosphatidylethanolamine antibodies than between RPLs and antibodies to anionic phospholipids for early gestational losses. Our data suggest that antiphosphatidylethanolamine antibodies may be a risk factor in patients with early RPLs.

Anti-annexin V antibodies in patients with early pregnancy loss or implantation failures.

OBJECTIVE: To describe the prevalence of annexin V antibodies (aANX) in women with early recurrent pregnancy losses (RPLs) or recurrent IVF-ET failure. DESIGN: Retrospective data analysis. SETTING: Tokai University Hospital, Kanagawa, Japan. PATIENT(S): Two hundred thirty-eight patients with RPLs, 48 patients with recurrent IVF-ET failure and 179 nonpregnant and 120 pregnant control group women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): ELISA was used to measure autoantibodies to annexin V. RESULT(S): An ELISA system developed for aANX revealed a dose-dependent relationship between annexin V and aANX. The positive/negative cutoff was set at 7 multiples of the median based on the 99th percentile of normal nonpregnant control group patients. Patients with RPLs (5.5%) or recurrent IVF-ET failure (8.3%) had a significantly increased incidence of aANX (IgG) compared with normal nonpregnant (1.1%) or pregnant control group women (0), whereas the prevalence of aANX between both patient groups or between both control groups was not statistically different. Specificity was confirmed by absorption studies using annexin V and by immunoblots. CONCLUSION(S): Our data show that aANX are associated with both RPLs and IVF-ET failure. We propose that anti-annexin V antibodies should be considered a risk factor for these reproductive failures.

Antiplatelet treatment with cilostazol after stent implantation.

OBJECTIVES: To evaluate the efficacy of cilostazol, a new synthetic inhibitor of phosphodiesterase, in preventing stent thrombosis after successful implantation. DESIGN: Preliminary prospective study. SETTING: A single coronary care unit in Japan. PATIENTS: Elective, bailout, or primary stents were implanted in 85 consecutive patients with 93 lesions. Primary stent implantation was performed in 18 patients with acute myocardial infarction. Patients received 200 mg cilostazol and 243 mg aspirin after stenting. MAIN OUTCOME MEASURES: Stent thrombosis, major and minor complications, and side effects were assessed in the six months after stenting. RESULTS: Gianturco-Roubin stents were implanted in 37 lesions, Wiktor stents in 55, and Palmaz-Schatz stents in 27. Multiple stents were used in 26 lesions. There was no mortality, stent thrombosis related Q wave myocardial infarction, emergency bypass surgery, repeat intervention, or vascular complications in the six months of follow up. Acute or subacute closure did not occur after stenting. There were no serious side effects such as leucopenia and/or abnormal liver function for three months. Cilostazol was withdrawn in one patient because of skin rash. Patients who underwent primary stenting had no clinical events, such as acute or subacute thrombosis, or side effects. CONCLUSIONS: Cilostazol is an effective antiplatelet agent with minimum side effects after elective, bailout, or primary stent implantation.

Autoantibodies to kininogen-phosphatidylethanolamine complexes augment thrombin-induced platelet aggregation.

Autoantibodies to the zwitterionic phospholipid (PL), phosphatidylethanolamine (PE), have been described in patients with thrombotic disease. We have reported that certain anti-PE antibodies (aPE) are not specific for PE, but are directed to PE-binding plasma proteins, high molecular weight kininogen (HK) and low molecular weight kininogen (LK). Kininogens bind to platelets and inhibit thrombin-induced platelet aggregation. This inhibition is specific for thrombin because kininogens do not inhibit platelet aggregation induced by adenosine diphosphate (ADP), collagen or calcium ionophore. To date, a platelet kininogen receptor has not been described. We recently reported that purified kininogens bind to purified PE in vitro. This opens the possibility that kininogens can bind to platelets by virtue of exposed PE in the platelet membrane. We thus questioned if aPE can recognize platelet bound kininogens and negate their antithrombotic property. Our experiments support this possibility by demonstrating that exogenously added kininogen-dependent IgG aPE markedly increased thrombin-induced platelet aggregation in vitro but did not alter ADP-induced aggregation. In contrast, kininogen independent IgG aPE which recognized PE per se did not augment thrombin-induced platelet aggregation. These data support a hypothesis that kininogen dependent aPE may cause thrombosis in vivo due to disruption of the normal antithrombotic effects of kininogen.

Circulatory support with sympathetic amines in brain death.

In 12 cases of brain death, the cardiovascular effects and changes of transcutaneous PO2 (PtcO2) during infusion of various sympathomimetic amines were determined. The larger amounts of vasopressors were necessary to maintain the blood pressure at more than 100 mmHg. With norepinephrine and dopamine, marked increase in blood pressure, cardiac output, systemic vascular resistance and also PtcO2 were observed. On the other hand, dobutamine was not an effective pressor agent in those situations. Even with more than 10 times the routinely used concentration of dobutamine, difficulties were encountered in keeping the blood pressure above 100 mmHg in many cases studied. With the infusion of dobutamine, a marked increase in cardiac output and heart rate were observed with a decrease in systemic vascular resistance and a fall in PtcO2 values in many occasions. In brain death, norepinephrine and dopamine will be recommended as the pressor agents in clinical practice. The changes of PtcO2 closely followed the changes of arterial blood pressure and did not parallel the changes of cardiac output or of heart rate.

Changes of lung water and cardiovascular parameters during neurosurgical procedures associated with various types of infusion.

With the Swan-Ganz catheter and double indicator technique cardiovascular parameters and lung water were measured in 16 neurosurgical procedures. Five hundred millilitres of whole blood, Manitol or Fluosol-DA, or 1000 ml of lactate-Ringer solution was infused within 30 min, and various parameters were estimated and analysed. Extravascular lung water did not change with either solutions. Fluosol-DA showed the most powerful pressure effects. With whole blood and Fluosol DA, cardiac output and oxygen availability increased. Marked hemodilution was observed with the infusion of either Manitol, Fluosol-DA or lactate-Ringer solution, but only Fluosol-DA insured adequate oxygen supply to tissues by increase in oxygen capacity in blood. Fluosol-DA proved to be one of the suitable colloidal solutions to improve the hemodynamics and hemodilution during operation.

Coronary vasoreactivity to ergonovine after angioplasty: difference between the infarct-related coronary artery and the noninfarct-related coronary artery.

BACKGROUND: The vasoreactivity after direct percutaneous transluminal coronary angioplasty (PTCA) in patients with previous myocardial infarction remains unknown. We examined the constrictor response to ergonovine of the infarct-related coronary artery in comparison with that of noninfarct-related coronary artery after angioplasty. METHODS: Ergonovine was administered intravenously to 17 patients with previous myocardial infarction (group I) and to 21 patients with stable angina (group II) 1 year after PTCA. The effects of ergonovine on lumen diameter were analysed quantitatively at the PTCA segment, nonPTCA segment (proximal to the PTCA segment), and nonPTCA artery. RESULTS: The ergonovine-induced decrease in minimal lumen diameter at the PTCA segment was significant in group I (decrease from 2.12 +/- 0.56 to 1.39 +/- 0.74 mm, P < 0.01), but not in group II (decrease from 1.60 +/- 0.35 to 1.43 +/- 0.33 mm, NS). Patients in group I showed a constrictor response at the nonPTCA artery (decrease in diameter from 2.54 +/- 0.90 to 1.94 +/- 0.77 mm, P < 0.01), and a tendency to constrict at the nonPTCA segment (2.56 +/- 0.67 to 2.11 +/- 0.66 mm, P = 0.06), whereas those in group II showed no significant constrictor response to ergonovine at any of the three segments examined. The changes in diameter at the three segments in patients in group I were significantly greater than those in group II (all P < 0.01). Subtotal coronary spasm at the PTCA segment was provoked only in three patients in group I (18%). CONCLUSIONS: The constrictor response to ergonovine of the infarct-related coronary artery was enhanced compared with that of the noninfarct-related coronary artery. This difference in coronary vasoreactivity at the angioplasty segment may be due to previous hypersensitivity of the smooth muscle.

Survey of 1120 Japanese women with a history of recurrent spontaneous abortions.

Our recent 7-year clinical survey showed that among the 1120 women with repeated spontaneous abortions registered in this clinic, 2898 out of a total of 3216 pregnancies (90.1%) had terminated in spontaneous abortion. Among these wastages, 84.2% occurred before 12 weeks of gestation, and 11.1 percent occurred between 12 and 15 weeks. Through routine examination of reproductive wastage, 82 (9.9%) of the 825 Japanese couples examined were shown to have either a chromosomal abnormality or normal variants in the wife and/or husband, thus demonstrating no racial difference in the incidence of chromosomal abnormalities in infertile patients in comparison with studies performed in other countries. One hundred and forty-seven congenital uterine anomalies (14.7%) were found in 1000 hysterosalpingographies, and 12 of 148 examined females were positive for anti-cardiolipin antibody. 393 other females with no major abnormalities likely to induce spontaneous abortions were indicated for immunotherapy. Ample time spent on genetic counseling prevented further reproductive wastage, and ideal metroplasty resulted in a successful post-operative pregnancy course in more than 85% of cases. Immunosuppressant and anticoagulant therapy decreased the serum titer of anti-cardiolipin antibody, enabling pregnancies to be maintained to term. Immunotherapy utilizing the husband's lymphocytes also brought more than 80% of pregnancies to successful completion, with 200 deliveries achieved with this therapy. In contrast, 64.1% of pregnancies again terminated spontaneously in patients who were indicated for immunotherapy but did not receive treatment. The findings of the present study suggest that the causes of reproductive wastage, especially the etiology of early recurrent spontaneous abortion, are complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetic cardiac autonomic dysfunction: parasympathetic versus sympathetic.

BACKGROUND: Diabetic cardiac autonomic dysfunction often causes lethal arrhythmia and sudden cardiac death. 123I-Metaiodobenzylguanidine (MIBG) can evaluate cardiac sympathetic dysfunction, and analysis of heart rate variability (HRV) can reflect cardiac parasympathetic activity. We examined whether cardiac parasympathetic dysfunction assessed by HRV may correlate with sympathetic dysfunction assessed by MIBG in diabetic patients. METHODS AND RESULTS: In 24-hour electrocardiography, we analyzed 4 HRV parameters: high-frequency power (HF), HF in the early morning (EMHF), rMSSD and pNN50. MIBG planar images and SPECT were obtained 15 minutes (early) and 150 minutes (late) after injection and the heart washout rate was calculated. The defect score in 9 left ventricular regions was scored on a 4 point scale (0 = normal approximately 3 = severe defect). In 20 selected diabetic patients without congestive heart failure, coronary artery disease and renal failure, parasympathetic HRV parameters had a negative correlation with the sum of defect scores (DS) in the late images (R = -0.47 approximately -0.59, p < 0.05) and some parameters had a negative correlation with the washout rate (R = -0.50 approximately -0.55, p < 0.05). In a total of 64 diabetic patients also, these parameters had a negative correlation with late DS (R = -0.28 approximately -0.35, p < 0.05) and early DS (R = -0.27 approximately -0.32, p < 0.05). CONCLUSIONS: The progress of diabetic cardiac parasympathetic dysfunction may parallel the sympathetic one.

Exercise myocardial perfusion scintigraphy is useful for evaluating myocardial ischemia even in the elderly.

Pharmacologic stress testing is recommended to elderly patients as a valuable alternative to exercise testing. We examined whether exercise testing is as useful for evaluating myocardial ischemia in the elderly as in the young. The consecutive 1,508 patients who underwent exercise 201Tl single-photon emission computed tomography (SPECT) were divided into six age groups: 6-29 years (n = 56), 30-44 (n = 143), 45-54 (n = 311), 55-64 (n = 498), 65-74 (n = 402), and 75-88 (n = 98). Both heart rate and rate-pressure product at peak exercise were significantly lower in patients aged 75-88 than in the other five groups. The frequency of ischemic ST depression was higher in patients aged 75-88 than in those aged 6-74, although the difference was not significant. Moreover, the frequency of 201Tl transient defect was significantly higher in patients aged 75-88 than in those aged 6-74. On the other hand, the sensitivity of ischemic ST depression for 201Tl transient defect was similar among the six groups, but the specificity was significantly lower in patients aged 75-88 than in those aged 6-74. In conclusion, exercise 201Tl SPECT is useful for evaluating myocardial ischemia even in the elderly, but exercise electrocardiography has limitations such as lower specificity in the elderly than 201Tl SPECT.