Serum concentrations of intact type IV collagen in diabetics.

We developed a sandwich enzyme immunoassay for intact type IV collagen (IV-C) using two monoclonal antibodies as a marker of basement membrane metabolism, and examined the relationship between serum IV-C and diabetic complications. Serum IV-C was measured in 186 diabetics with or without clinical signs of retinopathy, neuropathy, and/or nephropathy, and 328 healthy subjects. Serum IV-C was significantly (P less than .01) higher in diabetics (mean +/- SE: 124.83 +/- 2.94 ng/ml) than in healthy subjects (73.32 +/- 1.42 ng/ml). In diabetics with microangiopathy, serum IV-C became higher as clinical signs worsened. Especially in diabetics with nephropathy, serum IV-C became higher with the elevation of blood urea nitrogen (BUN), serum creatinine, and beta 2-microglobulin. Serum IV-C level seems to be a useful marker for assessment of the activity or progression of diabetic microangiopathy, and for evaluation of therapeutic effects.

Serum type IV collagen concentrations in diabetic patients with microangiopathy as determined by enzyme immunoassay with monoclonal antibodies.

In long-term diabetes mellitus, thickening of basement membrane in capillaries and small vessels is a characteristic lesion and plays an important role in the progression of diabetic microangiopathy. We have developed a sandwich enzyme immunoassay for human serum type IV collagen peptide with monoclonal antibodies. Previous studies suggested that collagen levels reflect the activity of fibrogenesis in basement membrane. Serum type IV collagen levels were measured in 137 non-insulin-dependent diabetic patients (aged 50-75 yr) with or without clinical signs of retinopathy, nephropathy, and/or neuropathy and 110 healthy subjects (aged 50-75 yr) without serological abnormality. Serum concentrations of type IV collagen were significantly higher (P less than 0.01) in diabetic patients (mean +/- SE 124.1 +/- 4.1 ng/ml) than in healthy subjects (73.9 +/- 2.2 ng/ml) and were increased with the prevalence or incidence of diabetic complications. In the patients with diabetic microangiopathy, serum type IV collagen levels became higher as clinical signs worsened. Especially in the patients with diabetic nephropathy, serum type IV collagen levels became higher with elevation of blood urea nitrogen, serum creatinine, and serum beta 2-microglobulin but not urinary excretion of beta 2-microglobulin and N-acetyl-beta-glucosaminidase. These observations indicated that elevation of serum type IV collagen in diabetic nephropathy was related to glomerular filtration dysfunction rather than renal tubular dysfunction. However, the antigen, which can be detected by our assay system, did not exist in urine specimens of healthy subjects, and an intimate relationship was not observed between serum type IV collagen level and serum creatinine level.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemoglobin A1 in cirrhosis of the liver.

Patients with cirrhosis of the liver (LC group, n = 12) frequently have glucose intolerance secondary to hepatic dysfunction. We compared HbA1 levels and other measures of blood sugar control in the LC group with those in healthy controls (N group, n = 43), patients with diabetes mellitus (DM group, n = 36), or patients with chronic hepatitis without evidence of cirrhosis (CH group, n = 12). HbA1 levels and the mean values of fasting plasma glucose for the past month (FPG) were as follows: LC group 6.40 +/- 0.36 (mean +/- SEM)% and 130 +/- 20 mg/dl, DM group 10.29 +/- 0.45% and 172 +/- 11 mg/dl, CH group 10.70 +/- 0.86% and 176 +/- 21 mg/dl, N group 6.52 +/- 0.11% and 83 +/- 1 mg/dl, respectively. HbA1 in the LC group was similar to that in the N group, although FPG in the former was higher (p less than 0.05). All groups showed statistically significant positive correlations between HbA1 levels and (a) FPG, (b) the daily profile of plasma glucose values, (c) the total or peak plasma glucose values during a 50 g-OGTT. The regression line in the LC group, however, was statistically different from that in DM or CH group. Thus, HbA1 in the LC group is lower than that in DM or CH in spite of equivalent glucose intolerance. Therefore, we suggest caution in the interpretation of HbA1 levels in hepatic cirrhosis.

Diabetic neuropathy as a heterogeneous syndrome: multivariate analysis of clinical and neurological findings.

We quantitatively assessed peripheral and autonomic nerve function in diabetic patients and compared them with various parameters of their diabetic status. Motor and sensory nerve conduction velocity (MCV, SCV), vibratory perception threshold (VPT) and the coefficient of variation of the ECG R-R interval (CV R-R) were measured in 85 diabetic patients aged 20-59 years. These values were compared with those of age-matched healthy subjects. Moreover, in 53 patients, MCV, SCV, VPT and CV R-R were investigated by multivariate analysis in relation to clinical parameters. In diabetics, MCV, SCV and CV R-R were significantly lower and VPT was higher than in age-matched healthy controls. The prevalence of impaired values in diabetics was 70% for VPT in the toe, 60% for SCV, and 55% for MCV, CV R-R and VPT in the finger. Impairments of MCV, SCV, CV R-R and VPT were closely correlated with diabetic retinopathy, proteinuria and duration of disease. Categorical regression analysis (multivariate analysis) revealed that the impairment of conduction velocity was closely related to diabetic retinopathy and to hypo- or areflexia, that the impairment of the vibratory perception threshold was related to ischemic changes in ECG and to hypo- or areflexia, and that the reduction of CV R-R was related to orthostatic hypotension and to proteinuria. These findings suggest that diabetic neuropathy progresses in parallel with other complications, and that it is a heterogeneous syndrome rather than a single entity.

[Peripheral somatic and autonomic nerve functions in patients with occupational vibration disease].

In order to evaluate the functions of the peripheral somatic nerve and autonomic nerve in patients with occupational vibration disease objectively and quantitatively, four examinations were performed on twenty 44-63 yr old patients with occupational vibration disease and their total operating time ranged from 5,000 to 43,750 h. 1) Motor nerve conduction velocities (MCV) and sensory nerve conduction velocities (SCV) of the ulnar and median nerves were measured using conventional methods. 2) Electrogustatory thresholds under the controlled area of the chorda tympani nerve were measured by Tomita's method using an electrogustometer (610-M, M.E.C.). 3) Dopamine-beta-hydroxylase (DBH) activity in blood was assayed by the photometric assay of Nagatsu and Udenfriend. 4) Coefficient of variation of R-R interval in ECG (CVR-R) was measured after 15-min-resting in supine position by using a R-R interval analyzer (Autonomic R 100, M.E.C.). The results of these examinations were compared with those of special examinations for the diagnosis of vibration disease. In patients with occupational vibration disease, MCV and SCV of the ulnar and median nerve were lower in value than those in age-matched healthy controls. In particular, MCV of the ulnar nerve, MCV and SCV of the median nerve were significantly lower in the patients than in the controls. Nerve conduction velocities were significantly correlated with skin temperature and nailpress test, though diminished nerve conduction velocities observed in vibration disease patients were considered to be attributable to peripheral circulatory disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)

[Auditory brainstem responses and electroencephalographic findings in patients with occupational vibration disease].

To evaluate the function of the central nervous system of patients with occupational vibration disease, electroencephalograms and auditory brainstem responses (ABR) were recorded in 20 male subjects with occupational vibration disease whose age ranged from 46 to 67 years (mean 57.4 yr). All the subjects had operated chain saws from 10 to 25 yr (mean 15.2 yr) and had frequently complained of many subjective symptoms induced by central nervous system disturbances such as headache, head heaviness, tinnitus, vertigo, and insomnia, which corresponded to stage 3 in the diagnostic criteria of Andreeva-Galanina. Twenty-six healthy men whose age ranged from 40 to 67 yr (mean 53.0 yr) were selected as controls. Electroencephalograms were recorded with a 12-channel electroencephalograph, using unipolar and bipolar leads. Auditory brainstem responses were recorded by signal averaging technique using 100 microseconds alternating clicks. The stimuli were presented at 70 dB above threshold (SL) with a rate of 10 per second. The following results were obtained. 1. By electroencephalography, the incidence of diffuse alpha pattern, slow alpha wave and drowsy pattern was 32%, 32%, and 42%, respectively. 2. Click thresholds in the patients were obviously higher than those in the healthy controls. 3. The occurrence rate of wave II of ABR in the patients (61.8%) was significantly lower than that in the healthy controls (85.0%) (p less than 0.05). 4. The interpeak latencies I-V and III-V of ABR in the patients were significantly longer than those in the healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Radioreceptor assay for beta-adrenergic receptor-reactive catecholamines in serum samples.

A procedure for effective application of ultrafiltration is described for preparation of serum catecholamine samples suitable for a sensitive radioreceptor assay. Each of the fresh serum samples unsuitable for the direct receptor assay was dialyzed by applying centrifugal force into a capsule-shaped porous core whose surface was tightly covered with a molecular filtration membrane. Interfering macromolecular serum components were left outside the capsule during the centrifugation or forced dialysis. The ultrafiltrate in the capsule was readily recovered by another centrifugation, and was found satisfactory as an assay specimen. In the radioreceptor assay system adapted to detect 30 pg per assay tube, epinephrine added to fresh serum to make the final concentration approximately 1 X 10(-8) mol/L was recovered semiquantitatively. Serum catecholamine level determined was equivalent to beta-adrenergic receptor reactivity that could be expressed in terms of (-)-epinephrine concentration.

Development of parathyroid adenoma in a case of chronic renal failure suggesting tertiary hyperparathyroidism.

A case of tertiary hyperparathyroidism with a parathyroid adenoma and hyperplasia was described as the first report in Japan. A 24-year-old man manifesting hypercalcemia had been treated with hemodialysis for 9 years. On admission, clubbed fingers richitic rosaries and a palpable node in the neck were the major physical findings. Laboratory examinations revealed hypercalcemia had elevated levels of plasma parathyroid hormone (PTH) in a c-terminal assay. Nevertheless the levels of PTH found by a n-terminal assay disclosed an only small increase. The PTH levels were scarcely decreased after a bolus injection of calcium gluconate. A large tumor corresponding to the palpable node was resected. Histologically, the tumor was an adenoma with thick fibrous capsule and interparenchymal bands. Other parathyroid glands showed secondary clear cell hyperplasia without signs of cellular hyperactivity.