123I-MIBG myocardial scintigraphy in diabetic patients: relationship to autonomic neuropathy.

The aim of this study was to investigate the relationship between autonomic nerve dysfunction and myocardial uptake of 123I-meta-iodobenzyl guanidine (MIBG) in patients with diabetes mellitus. Twenty-two non-insulin-dependent diabetic patients, 9 with autonomic neuropathy [ANP(+)] and 13 without autonomic neuropathy [ANP(-)], and 8 controls were included in the study. Both planar and single photon emission tomographic (SPET) images were obtained 30 min (early) and 3 h (delayed) after the 123I-MIBG injection. The heart-to-mediastinal uptake ratio (H/M) and the washout ratio of 123I-MIBG (%WR) were calculated from planar images. The uptake ratio of the inferior wall to the anterior wall (I/ A) and the %WR of both the inferior and anterior walls were calculated from the SPET images. On the early plantar images, the mean H/M ratio in the ANP(+) group was significantly lower than that of the control group. The mean %WR on the planar images in the ANP(-) group was significantly higher than that of the controls. The SPET images demonstrated a reduction in MIBG uptake and significantly increased clearance in the inferior wall of the ANP(-) patients. These findings extended to other areas of the heart in the ANP(+) patients. In the quantitative analysis of the SPET images, the ANP(+) group had significantly lower I/A values and significantly higher %WR values in the anterior wall. The ANP(+) group showed significantly increased clearance of 123I-MIBG in the inferior wall. We conclude that 123I-MIBG myocardial scintigraphy is a useful diagnostic tool both in the early detection and evaluation of the progression of myocardial sympathetic nerve dysfunction in patients with diabetes mellitus. Both the I/A and %WR calculated from SPET images are useful parameters.

[123I-MIBG myocardial scintigraphy in diabetic patients: association with autonomic neuropathy].

123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in 20 diabetic patients (NIDDM) and 8 control subjects to investigate the association between clinical autonomic nerve dysfunction and myocardial accumulation of MIBG. We used coefficient variance of R-R interval (CVR-R) as a index of the autonomic neuropathy and categorized diabetes into two groups (CVR-R > or = 2.0: non-autonomic neuropathy. CVR-R < 2.0: autonomic neuropathy). In planar imaging studies, heart to mediastinum MIBG uptake ratio (H/M) was calculated on both early and delayed images. The washout ratio of 123I-MIBG in the heart (%WR) was also obtained using myocardial tracer activity on the both images. Mean value of these indices in diabetic group did not reveal any significant difference with the value in the control group. On the SPECT images, low uptake was observed in the posterior-inferior wall with normal uptake of 201Tl in diabetic patients with non-autonomic neuropathy. These areas extended in patients with autonomic neuropathy. The mean value of count ratio of posterior-interior to anterior wall (posterior-inferior/anterior ratio: PI/A) in the diabetic autonomic neuropathy group was significantly higher than in the control group on the both early and delayed images. And the mean value of regional %WR in the posterior-inferior wall calculated by the both MIBG SPECT images was significantly higher in the non-autonomic neuropathy group than in the control group. In the diabetic patients, retention mechanism of 123I-MIBG was considered to be involved at an early stage without autonomic nerve dysfunction clinically. As autonomic neuropathy progressed severely, uptake mechanism was also supposed to be involved. Therefore, 123I-MIBG myocardial scintigraphy was useful for early detection of cardiac sympathetic nervous dysfunction in diabetic patients.

Family of a patient with serum cholinesterase deficiency.

A-39-year-old man was admitted to our hospital because of a markedly decreased level of serum cholinesterase found incidentally by a blood test. Detailed examination did not reveal severe liver disease, malignant tumor, infection or organophosphate compound poisoning. Investigation of three generations of his family revealed two homozygous and five heterozygous family members with the cholinesterase deficiency gene E1s indicating familial serum cholinesterase deficiency.

Islet amyloid polypeptide (IAPP) and pancreatic islet amyloid deposition in diabetic and non-diabetic patients.

Twenty pancreata of non-diabetic patients and 17 pancreata of diabetic patients, including two patients with insulin-dependent diabetes mellitus, were immunohistochemically studied using antiserum against human islet amyloid polypeptide (IAPP). The islet beta cells in non-diabetic patients were immunoreactive for both IAPP and insulin. Amyloid deposition immunoreactive for IAPP was detected in six of 20 pancreata of non-diabetic patients. The plasma glucose level of three of these six patients was elevated to more than 200 mg/dl, and that of the other three ranged from 143 to 162 mg/dl; all six were receiving intravenous hyper-alimentation and had no history of diabetes prior to treatment. Amyloid deposition was present in all patients with non-insulin-dependent diabetes mellitus (NIDDM). The deposition was absent in the pancreata of two secondary diabetic patients, one of whom had received steroid hormone for bronchial asthma and the other of whom had liver cirrhosis with hepatocellular carcinoma; deposition was also absent in the pancreas of a patient with impaired glucose tolerance diagnosed on a 75-g oral glucose load. Heterogeneous expression of immunoreactivities of beta cells for insulin and for IAPP was present, suggesting independently regulated production and secretion of the peptides. Immunoreactivity of beta cells was more sensitively decreased for IAPP than for insulin in the islets of NIDDM patients. The decreased immunoreactivity for IAPP suggested an initial stage of disturbed beta-cell function, even if the immunoreactivity for insulin was apparently intact or the amyloid deposition in the islets was insignificant. The degree of amyloid deposition immunoreactivity for IAPP did not necessarily reflect the severity of diabetes mellitus. Amyloid deposits were seen at the narrow spaces beneath the insular capsule of connective tissues and the perivascular region or, in some cases, occupying the whole of the islet. The diabetogenic role of IAPP is unclear, but the deposition might be an accelerating factor which disturbs beta-cell function.

Molecular forms of atrial natriuretic polypeptides circulating in human plasma.

Molecular forms of atrial natriuretic polypeptides circulating in human plasma were analyzed by chromatographic separation, coupled with radioimmunoassay. Analyses were done with human plasma samples taken from 24 human subjects, divided into groups of healthy volunteers, patients with renal disease, and patients with heart disease, with 8 subjects in each group. Although alpha-hANP was found as a major circulating form in most of the plasma specimens (16 cases), beta-hANP accompanied by alpha-hANP was found in 6 cases including 2 healthy volunteers. In addition, hANP-immunoreactive macromolecule, which is likely a bound form of hANP, was found to some extent in all the specimens tested. Diversity of human plasma in ANP molecular distribution was discussed in connection with a radioimmunoassay for plasma ANP.

Increased release of atrial natriuretic polypeptides in rats with DOCA-salt hypertension.

This study compared atrial and plasma concentrations of immunoreactive alpha-rat atrial natriuretic polypeptide (i alpha-rANP) in rats given tap water (control), a 1% saline solution (salt), deoxycorticosterone acetate (DOCA) and DOCA plus 1% saline solution (DOCA-salt) after 1 and 8 weeks of treatment. DOCA (100 mg/kg) was given by implanting a piece of silicon rubber impregnated with DOCA subcutaneously. Atrial i alpha-rANP increased, while plasma i alpha-rANP decreased with time in all groups. Atrial concentration of i alpha-rANP was significantly lower in the DOCA-salt group than in the other groups at 1 week, and was reduced in the DOCA and DOCA-salt groups as compared to the control group at 8 weeks. On the other hand, plasma concentration of i alpha-rANP was significantly higher in the DOCA and the DOCA-salt groups than in the control group at 1 week; the DOCA and DOCA-salt group values were also higher than the control and salt group values at 8 weeks. Atrial concentration of i alpha-rANP was inversely correlated with systolic blood pressure in the all rats at 1 week (r = 0.48, p less than 0.001) and at 8 weeks (r = 0.33, p less than 0.05). Plasma concentration of i alpha-rANP was positively correlated with systolic blood pressure at 8 weeks (r = 0.37, p less than 0.05). In addition, there was a significant positive correlation between plasma/atrial ratio of i alpha-rANP concentration and systolic blood pressure at either stage (r = 0.41, p less than 0.01 at 1 week; r = 0.40, p less than 0.01 at 8 weeks). Thus, it seems likely that the release of ANPs is increased in response to expansion of extracellular fluid volume or elevation of blood pressure, modifying the development of hypertension in DOCA-salt rats.

Molecular forms of atrial natriuretic polypeptides in mammalian tissues and plasma.

A highly sensitive radioimmunoassay detecting for all the atrial natriuretic polypeptides isolated so far from human and rat (hANPs and rANPs) has been established by using an antiserum raised against alpha-hANP, since the antiserum recognizes the subsequence flanked by two cysteine residues (positions 7 and 23) in alpha-hANP and crossreacts with human as well as rat ANPs. By using the radioimmunoassay combined with gel chromatography or high performance liquid chromatography, it was revealed that ANP immunoreactivity in human atria is composed of alpha-(28 residues), beta-(56 residues: alpha-hANP dimer) and gamma-hANP(126 residues) in various ratios. In rat, porcine and bovine atrial tissues, however, gamma-rANP(126 residues) was found to be a major component. In contrast with atrial ANP, plasma ANP was found to be predominantly alpha-form in rat.