Restoration of a Microdont Using the Resin Composite Injection Technique With a Fully Digital Workflow: A Flexible 3D-printed Index With a Stabilization Holder.

Direct composite restorations are accepted as a treatment option for microdontia, which is a relatively prevalent condition that poses esthetic concerns. While free-hand composite placement is technique-sensitive and time-consuming, the resin composite injection technique is more straightforward and predictable. A fully digital workflow has been recently introduced, but the 3D-printed resin index is rigid and challenged by undercuts, as opposed to the silicone index. This case report presents a flexible 3D-printed resin index, which can accurately transfer the digitally simulated functional and esthetic form to the final restoration. In addition, a rigid stabilization holder was designed to stabilize the flexible index.

Neoadjuvant chemotherapy and hormonal therapy followed by radical prostatectomy: feasibility and preliminary results.

PURPOSE: We assessed the feasibility and efficacy of integrating chemotherapy and androgen ablation with radical prostatectomy in patients with locally advanced prostate cancer. The neoadjuvant approach was adopted because it allows an in situ assessment of antitumoral activity. PATIENTS AND METHODS: Thirty-three patients were enrolled who met the clinical criteria of stage T1-2, Gleason score of >/= 8 or T2b-T2c, Gleason score of 7 and prostate-specific antigen (PSA) level greater than 10 ng/mL (n = 15), or clinical stage T3 (n = 18). Therapy consisted of 12 weeks of ketoconazole and doxorubicin alternating with vinblastine, estramustine, and androgen ablation followed by prostatectomy. The ability of neoadjuvant chemotherapy and hormonal therapy to induce a 20% rate of pT0 in the prostatectomy specimen as well as surgical feasibility were assessed. RESULTS: Chemotherapy complications were comparable to those reported with this regimen previously. No major intraoperative complications occurred. Postoperative complications occurred in 10 (33%) of 30 patients. One patient died at home after discharge (postoperative day 17; no autopsy was performed). Ten (33%) of the 30 patients had organ-confined disease, and 20 (70%) of 30 had extraprostatic extension; 11 (37%) of the 30 had positive lymph nodes. Only five (17%) of 30 exhibited positive surgical margins. All patients achieved an undetectable PSA level postoperatively, and 20 of the surviving 29 patients remain without disease recurrence with a median follow-up of 13 months (range, 9 to 18 months). CONCLUSION: Chemotherapy and androgen ablation followed by radical prostatectomy was feasible in patients with locally advanced prostate cancer. Although the goal of achieving a 20% rate for pT0 status was not achieved, we believe this type of integrated therapeutic strategy should be investigated further for its ability to alter the course of regionally advanced prostate cancer.

Evaluation of PSF1 as a prognostic biomarker for prostate cancer.

BACKGROUND: Partner of SLD5 1 (PSF1) is an evolutionarily conserved DNA replication factor. Previous studies have suggested that transcriptional activity of the PSF1 gene correlated with malignancy of cancer cells. The objective of the current study was to evaluate the relationship between PSF1 expression and the clinical features of prostate cancer. METHODS: We determined the expression of PSF1 in 120 needle biopsy samples of prostate cancer by immunohistochemistry. We divided patients into PSF1-positive or -negative groups and analyzed the relationships between the expression of PSF1, the Gleason score, PSA level, TNM classification and prognosis. RESULTS: Our results showed that the PSF1 expression correlated significantly with PSA values at diagnosis (P=0.0028), with tumor grade (P<0.0001), and with clinical stage (P=0.0005). Moreover, the PSF1 expression correlated significantly with overall survival (hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.17-15.8; P=0.003) and progression-free survival in 99 consecutive patients with prostate cancer. Noteworthy, the prognosis of PSF1-positive cases was also worse in patients with a Gleason score of 8-10 (HR 3.7; 95% CI 1.28-13.43; P=0.0143). Limitations include that this study had a retrospective design, that patients in the study were heterogeneous and included those with early and advanced cancer, and that small tumor fragments may not be representative of the entire carcinoma. CONCLUSIONS: PSF1 is expressed in high-grade prostate cancer and may be a useful biomarker to identify patients with a poor prognosis at the time of diagnosis.

Reduction of hypothalamic norepinephrine does not alter the osmoregulation of vasopressin in rats.

The supraoptic nuclei of the hypothalamus are known to be heavily innervated by noradrenergic neurons. However, the role of these neurons in regulating secretion of the antidiuretic hormone, arginine vasopressin, remains unsettled. In an effort to clarify this question, we studied the effect of multiple small doses of D,L alpha-methyl-p-tyrosine (alpha-MpT) on hypothalamic norepinephrine and the osmoregulation of vasopressin in rats. We found that, at the doses employed (80 mg/kg every 6 h for 24 h), alpha-Mpt reduced mean (+/- SD) hypothalamic norepinephrine by about 50% but did not affect plasma osmolality, sodium, glucose, urea, or vasopressin either under basal conditions or during osmotic stimulation by ip injection of hypertonic saline. During the latter, plasma vasopressin correlated directly with plasma osmolality and the regression lines that described the relationships in the control and drug-treated rats were identical. Hematocrit and mean arterial pressure were also unaffected by alpha-MpT. These findings do not support the concept based on previous studies that central noradrenergic pathways mediate the vasopressin response to osmotic stimuli.

Regulation of matrix metalloproteinases (MMP-2, -3, -9, and -13) by interleukin-1 and interleukin-6 in mouse calvaria: association of MMP induction with bone resorption.

Interleukin-1 (IL-1) greatly induces osteoclast formation and stimulates bone resorption of mouse calvaria in culture. In the presence of soluble IL-6 receptor (sIL-6R), IL-6 similarly induces osteoclast formation, but the potency of IL-6 in inducing bone resorption in organ culture is weaker than that of IL-1. To study the differences in bone-resorbing activity between IL-1 and IL-6, we examined the effects of the two cytokines on the induction of matrix metalloproteinases (MMPs). In mouse calvarial cultures, IL-1 markedly enhanced the messenger RNA (mRNA) expression of MMP-13 (collagenase 3), MMP-2 (gelatinase A), MMP-9 (gelatinase B), and MMP-3 (stromelysin 1), which associated with increases in bone matrix degradation. A hydroxamate inhibitor of MMPs significantly suppressed bone-resorbing activity induced by IL-1. Gelatin zymography showed that both pro- and active-forms of MMP-2 and MMP-9 were detected in the conditioned medium collected from calvarial cultures, and IL-1 markedly stimulated both pro- and active-forms of the two gelatinases. IL-6 with sIL-6R also stimulated mRNA expression and biological activities of these MMPs, but the potency was much weaker than that of IL-1. Conditioned medium collected from IL-1-treated calvariae degraded native type I collagen, but 3/4- and 1/4-length collagen fragments were not detected, suggesting that both collagenases and gelatinases synergistically degraded type I collagen into smaller fragments. In mouse osteoblastic cells, the expression ofMMP-2, MMP-3, and MMP-13 mRNAs could be detected, and they were markedly enhanced by IL-1alpha on days 2 and 5. IL-6 with sIL-6R also induced expression of MMP-13 and MMP-2 mRNAs on day 2, but the expression was rather transient. These results demonstrate that the potency of induction of MMPs by IL-1 and IL-6 is closely linked to the respective bone-resorbing activity, suggesting that MMP-dependent degradation of bone matrix plays a key role in bone resorption induced by these cytokines.

Hyponatremia and osmoregulation of vasopressin secretion in patients with intracranial bleeding.

To clarify the cause and pathophysiology of hyponatremia after intracranial bleeding, we analyzed the possible causative factors, and examined the response of vasopressin (AVP) secretion to osmotic stimulus in six patients. Despite hyponatremia, urinary sodium excretion persisted, with urinary osmolality exceeding plasma osmolality. Serum levels of urea nitrogen, creatinine, and uric acid were not elevated in any of them. PRA was normal or subnormal in four patients, and all had normal adrenocortical and thyroid functions. Although these laboratory findings may support the diagnosis of the syndrome of inappropriate antidiuretic hormone secretion, the cause of hyponatremia in our patients was attributed to excessive renal excretion of sodium, because water load performed in an euvolemic state showed no impairment in diuresis, and replenishment of sodium without water restriction improved hyponatremia as well as clinical conditions. Plasma AVP levels relative to plasma osmolality in these patients were constantly elevated. When challenged by an osmotic stimulus, AVP secretion increased with increasing plasma osmolality in one patient, but no consistent pattern of AVP secretion was observed in others. The potentiating effect of hypovolemia on osmotic secretion of AVP was not demonstrated in any of the patients. These results show that hyponatremia after intracranial bleeding with clinical features almost indistinguishable from those of syndrome of inappropriate antidiuretic hormone secretion may result from an impaired renal sodium-conserving mechanism of unknown cause. Persistent AVP secretion without an alteration in the sensitivity of the osmostat in this pathological state may be due to an incomplete suppression by plasma hypotonicity per se of the baroreceptor-mediated stimulation of AVP release.

Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients with adrenal insufficiency.

To clarify the mechanism underlying abnormal vasopressin (AVP) secretion in glucocorticoid deficiency, we examined the response of AVP secretion to osmotic stimulus produced by 5% saline infusion and analyzed the possible causative factors in seven patients with hypoosmolal hyponatremia resulting from adrenal insufficiency. In all patients, urinary sodium excretion persisted with urine osmolality exceeding plasma osmolality, and plasma AVP levels relative to plasma osmolality were elevated. Blood urea nitrogen, plasma creatinine, and PRA ranged from low to normal. All patients had nausea or vomiting, three had hypotension, and two had hypoglycemia; however, the primary cause of increased AVP secretion was attributed to none of these stimuli. After 5% saline infusion, patterns of changes in plasma AVP levels in individual patients were variable: levels decreased with increasing plasma osmolality in two patients and remained unchanged in the other five patients. Despite hyponatremia and absence of hypovolemia, thirst was present in the five patients, who responded normally to questions. This abnormality in AVP secretion and thirst was corrected after glucocorticoid replacement with normalization of plasma sodium concentrations and osmolality. Thus, glucocorticoid deficiency in man results in a clinical picture almost indistinguishable from that of the syndrome of inappropriate secretion of antidiuretic hormone. Persistent AVP secretion in this pathological state is due to a loss of hypotonic suppression of the osmostat for AVP release, which may be occasioned primarily by glucocorticoid deficiency per se and aggravated secondarily by multiple nonosmotic stimuli including nausea, hypotension, and hypoglycemia.

Studies of thyroid function and immune parameters in patients with hyperthyroid Graves' disease in remission.

The natural course of hyperthyroidism due to Graves' disease after discontinuation of antithyroid drug therapy was studied in 184 patients who had been treated with methimazole and whose thyroid function was suppressible with T3 when methimazole was discontinued. The patients were followed after discontinuation of therapy for up to 60 months. Serum T4, free T4 (FT4) and T3 levels, TSH receptor antibody (TRab) and anti-DNA antibody titers, and the percentage of HLA-DR positive lymphocytes in peripheral blood were measured serially. TRab and anti-DNA antibody tests were positive in the majority of patients before treatment and were negative in most at the end of treatment. Twenty-three (12.5%) patients had a recurrence of their hyperthyroidism, which occurred a mean of 20 months after withdrawal of methimazole; they are designated as having overt recurrent hyperthyroidism (group A). In these patients, serum T4, FT4 and T3 concentrations increased rather abruptly to markedly elevated levels in a several-month period and the TRab and anti-DNA antibody titers increased markedly at or shortly after recurrence in the majority. In 9 patients (4.1%), TRH-induced TSH secretion became totally suppressed, indicating the reappearance of thyroidal autonomy; however, the patients did not have any hyperthyroid signs and symptoms (subclinical hyperthyroidism; group B). Their serum T4 and FT4 concentrations fluctuated in the upper normal to slightly supra-normal range, and their serum T3 concentrations remained within the normal range throughout the follow-up period, but their TRab and anti-DNA antibody titers did not appreciably increase. Thus, the time of recurrence could not be precisely determined in group B. In the remainder (152 patients; 83.4%), serum thyroid hormone levels and TRH-induced TSH secretion remained normal, TRab and anti-DNA antibody titers remained negative, and hyperthyroidism did not recur (euthyroid remission; group C). At the time of final examination (in groups B and C) or at the time of recurrence (in group A), the percentage of HLA-DR positive peripheral lymphocytes was 17.9% in group A, 15.9% in group B, and 12.1% in group C. Retrospective analysis of the data indicated that the mean pretreatment TRab titer (percent inhibition of TSH binding) was slightly but not significantly lower in group C (37.8%) compared to those in group A (53.9%) and group B (54.8%). The 3 groups were indistinguishable by all other laboratory data both before treatment and at the time of the T3 suppression test. These data strongly indicate heterogeneity among patients with hyperthyroidism due to Graves' disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship between plasma atrial natriuretic peptide levels and atrial pressure in man.

In an attempt to clarify the mechanisms regulating the release of atrial natriuretic peptide (ANP) in man, ANP levels in pulmonary arterial plasma determined by RIA were correlated to hemodynamic variables in 17 patients with heart disease who underwent cardiac catheterization and angiocardiography. In addition, plasma ANP levels in various blood vessels were determined in 7 patients with heart disease and in 7 normal subjects to determine the source and the site of removal of circulating ANP. A significantly positive correlation was found between plasma ANP levels and mean pulmonary arterial wedge pressure, while the correlation between plasma ANP levels and mean right atrial pressure was not significant. After the injection of contrast medium, both mean right arterial pressure and plasma ANP levels increased, and a significant positive correlation was found between the two variables. When ANP levels in plasma collected from various blood vessels were compared, the highest levels were found in the coronary sinus. Plasma ANP levels in the renal vein were the lowest and were 50% of the levels in the aorta. Plasma ANP levels in the superior vena cava and internal jugular vein were higher than that in the antecubital vein. Analysis of immunoreactive ANP in pooled plasma by high performance liquid chromatography revealed that the retention time of the main ANP peak coincided with that of synthetic human alpha ANP. These results indicate that circulating ANP mainly originates from the heart, the kidney rapidly takes up a significant amount of ANP from the circulation, and an increase in both left and right atrial pressure triggers ANP release in man.

Acute aquaresis by the nonpeptide arginine vasopressin (AVP) antagonist OPC-31260 improves hyponatremia in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

The present study was undertaken to determine whether the non-peptide V2 arginine vasopressin (AVP) antagonist 5-dimethylamino- 1[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepi ne hydrochloride (OPC-31260) produces water diuresis and improves hyponatremia in patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Eleven patients (9 males and 2 females, 64 +/- 3.5 yr) with SIADH were included in the present protocol, which was comprised of 3 successive days. Day 1 was a control day, and on days 2 and 3 OPC-31260 was administered intravenously. Five blood and urine collections were made at 1-2 h intervals during the 6 h observation period each day. A single administration of 0.25 and 0.5 mg/kg OPC-31260 increased the 4 h cumulative urine volume and decreased urinary osmolality to below 225 mOsm/kg H2O. Such a diuretic effect was independent of an increase in urinary solute excretions. This aquaresis by 0.5 mg/kg OPC-31260 caused a significant increase in serum sodium level by approximately 3 mEq/L. The antagonistic effect of OPC-31260 lasted for 4 h when it was given intravenously. These results indicate that OPC-31260 is an effective therapeutic agent for hyponatremia in patients with SIADH.

Comparison of the responses in the nomifensine test with hyperprolactinemia due to prolactin-secreting pituitary tumors and nonprolactin-secreting hypothalamic tumors.

It has recently been proposed that nomifensine (Nom) administration discriminates those patients with PRL-secreting pituitary tumors from those who have hyperprolactinemia due to other causes. In the present study, this test was performed on 12 presumed functional hyperprolactinemic subjects, 9 patients with surgically proved PRL-secreting pituitary adenoma (6 microadenoma and 3 macroadenoma), and 7 patients with surgically proved non-PRL-secreting hypothalamic tumors (3 craniopharyngioma, 3 suprasellar germinoma, and 1 suprasellar ependymoma). The Nom test suppressed the plasma PRL level to below 60% of the basal level in all 12 women with presumed functional hyperprolactinemia, but did not alter plasma PRL levels in the patients with PRL-secreting pituitary adenoma or hypothalamic tumor. This evidence confirms that the test is, at least in part, able to discriminate those individuals with PRL-secreting pituitary adenoma from those without, regardless of the size of the tumor. However, the test is not capable of distinguishing between hyperprolactinemia due to PRL-secreting pituitary tumors and that due to non-PRL-secreting hypothalamic tumors. A lack of response to Nom is not necessarily due to the presence of a PRL-secreting tumor, and may be related to dysfunction to the hypothalamic-pituitary system.

Atrial natriuretic peptide in patients with the syndrome of inappropriate antidiuretic hormone secretion and with diabetes insipidus.

To examine a possible role for atrial natriuretic peptide (ANP) in water and sodium metabolism disturbances associated with abnormal vasopressin (AVP) secretion, we measured plasma ANP concentrations in 15 patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and in 17 patients with central diabetes insipidus (DI). The mean plasma ANP concentration (30.2 +/- 10.4 pmol/L) in SIADH patients who had hyponatremia, plasma hypoosmolality, hyperosmolar urinary compared to plasma sodium levels, and increased plasma AVP levels relative to plasma osmolality was significantly higher than that in normal subjects (12.6 +/- 4.9 pmol/L), although there was a considerable individual variation in plasma ANP ranging from normal to clearly elevated levels (15.1-47.0 pmol/L). When hyponatremia was corrected by water restriction or demeclocycline administration, plasma ANP levels decreased significantly and fell into the normal range (12.5 +/- 4.3 pmol/L). DI patients who complained of polyuria and polydipsia and had hypoosmolar urine, normal or elevated plasma sodium concentrations, and decreased plasma AVP levels relative to plasma osmolality, on the other hand, had a significantly lower mean plasma ANP level (7.6 +/- 2.9 pmol/L) than normal subjects. There was, again, a considerable overlap between plasma ANP levels in individual DI patients (4.2-13.9 pmol/L) and those in normal subjects. Treatment with 1-desamino-8-D-arginine vasopressin resulted in a significant increase in the mean plasma ANP level (18.6 +/- 8.0 pmol/L). There were no significant correlations between plasma ANP and AVP levels in either group of patients. The results indicate that ANP secretion is modulated by changes in plasma volume consequent to abnormal AVP secretion, which may have a pathophysiological significance in maintaining volume homeostasis.

Advances in the application of prostate-specific antigen in the detection of early-stage prostate cancer.

Prostate-specific antigen (PSA) has revolutionized the detection of prostate cancer. PSA-based screening has been shown to be effective in detecting prostate cancer at an early, potentially curable stage; however, this tumor marker is limited by appreciable false-positive and false-negative results. This is especially problematic when the PSA level is in the upper limit of normal (2.5 to 4.0 ng/mL) or the intermediately increased range (4.1 to 10.0 ng/mL). Several PSA-related indexes and assays have been proposed in an attempt to improve the power of PSA in the early detection of prostate cancer: PSA density (PSAD), age-referenced PSA, volume-referenced PSA, PSAD of the transition zone (PSA-TZ), ProstAsure Index, (Global Health Net, Savannah, GA) and percent free PSA. These indexes may improve the sensitivity and specificity of PSA-based screening, facilitating the early detection of prostate cancer and reducing the number of unnecessary biopsies.

Correlation of histological inflammation in needle biopsy specimens with serum prostate- specific antigen levels in men with negative biopsy for prostate cancer.

OBJECTIVES: To reveal the possible contribution of histological inflammation within the prostate to the abnormal elevation of serum prostate-specific antigen (PSA) levels in patients with needle biopsy negative for prostate cancer. METHODS: We reviewed negative needle biopsy specimens obtained in 93 patients. The degree of acute and chronic inflammation as evaluated histologically was compared with serum PSA levels in conjunction with age and prostate volume. RESULTS: Both age (P <0.01) and prostate volume (P <0.0001) correlated significantly with serum PSA levels and were significantly greater in patients with abnormal serum PSA levels (greater than 4.0 ng/mL) than in those with normal serum PSA levels (4.0 ng/mL or less) (P <0.01). The presence of histological inflammation within the prostate also correlated significantly with serum PSA levels. Multiple regression analysis demonstrated prostate volume to be the only independent determinant of serum PSA levels (P <0.01). In patients with a prostate volume larger than 25 mL, only prostate volume correlated significantly with serum PSA levels (P <0. 05). On the other hand, the degree of acute inflammation as represented by polymorphonuclear leukocyte infiltration was the only parameter correlating significantly with serum PSA levels (P <0.05) in patients with a prostate volume smaller than 25 mL. CONCLUSIONS: Histologically defined acute inflammation within the prostate is a significant contributor to elevated serum PSA levels, especially in patients with small prostates. In the assessment of needle biopsy results negative for prostate cancer, it might be helpful to evaluate the degree of histological inflammation, especially in terms of the necessity of subsequent repeated biopsies.

Effect of nephrectomy on angiotensin II concentrations in plasma and hypothalamus of the dehydrated rat.

Bilateral nephrectomy in the rats deprived of water for 46 h markedly reduced plasma angiotensin II concentrations (P less than 0.001), but it was without effect on extremely low levels of the hormone in the hypothalamic tissue. These results may suggest that the activity of a possible intrinsic brain renin-angiotensin system is not influenced by that of the kidney-plasma renin-angiotensin system.

Significant decrease of the International Index of Erectile Function in male renal failure patients treated with hemodialysis.

In order to evaluate the erectile function in male renal failure patients treated with hemodialysis (HD), we investigated the International Index of Erectile Function (IIEF) in patients and healthy controls. The subjects were 174 male patients treated with HD, of whom 43 had diabetes mellitus (DM) and the remaining 131 patients did not have DM. The controls were 1133 healthy males. We evaluated the prevalence of erectile dysfunction (ED) using the erectile function (EF) score, which is one of the five domains of the IIEF, in each age group (upto 39 y old, 40-49 y old, 50-59 y old, 60-69 y old). The severity of ED was classified into five categories using EF in each age group. The univariate logistic regression analysis and multiple variate analysis of IIEF in HD patients were performed. The prevalence of ED in HD patients was significantly higher than that in the controls in each age group. The severity of ED in HD patients was also significantly higher than that in the controls in each age group. In the logistic regression analysis and multiple variate analysis of IIEF in HD patients, DM and age were significant risk factors on sexual dysfunction. ED was more prevalent in male renal failure patients treated with HD than in the controls. In the patient group, ED was more prevalent in older DM patients.

Endothelin-1 and big endothelin-1 in NIDDM patients with and without microangiopathy.

To examine a possible role for endothelin-1 in the pathophysiology of diabetic microangiopathy, we measured plasma levels of endothelin-1 and big endothelin-1, a precursor peptide of endothelin-1, in 33 untreated patients with non-insulin-dependent diabetes mellitus. There was no significant difference among the mean plasma endothelin-1 concentrations in 18 patients with microangiopathy, in 15 patients without microangiopathy and in 33 age-matched normal subjects. In contrast, the mean plasma big endothelin-1 concentration in patients with microangiopathy was significantly higher than in those without microangiopathy or in normal subjects. As a consequence, the mean big endothelin-1 to endothelin-1 ratio in patients with microangiopathy was significantly higher than in the other two groups. There was no significant correlation between plasma levels of endothelin-1 or big endothelin-1 and fasting blood glucose, HbA1c, mean blood pressure, or period of duration of diabetes mellitus in the patient groups. The results indicate that elevation of plasma big endothelin-1 levels with diminished conversion of big endothelin-1 to endothelin-1 is associated with diabetic microangiopathy, which may be the effect rather than the cause of endothelial dysfunction.

Thirst and plasma levels of vasopressin, angiotensin II and atrial natriuretic peptide in patients with non-insulin-dependent diabetes mellitus.

To clarify a possible mechanism whereby the perception of thirst may be associated with diabetes mellitus, we measured plasma levels of vasopressin (AVP), angiotensin II (ANG II), atrial natriuretic peptide (ANP) and plasma renin activity (PRA) in non-insulin-dependent (NIDDM) diabetic patients with or without thirst. Thirteen male NIDDM patients complaining of thirst had a significantly high blood hematocrit, plasma urea nitrogen and creatinine concentrations and plasma osmolality, indicating a reduction in plasma volume. In addition, the patients had a significantly high mean plasma concentrations of AVP (3.20 +/- 1.27 pmol/l) ANG II (33.8 +/- 31.4 pmol/l) and PRA, but a low mean plasma ANP concentration (8.9 +/- 4.5 pmol/l). After treatment with diet and/or sulfonylurea, plasma levels of AVP, ANG II and PRA decreased with a concomitant increase in plasma volume and disappearance of thirst. In contrast, 13 NIDDM patients (9 females and 4 males) without thirst had normal plasma urea nitrogen and creatinine concentrations, and the hematocrit did not change significantly after treatment. Plasma AVP (0.95 +/- 0.34 pmol/l), ANG II (14.7 +/- 8.8 pmol/l) and ANP (10.7 +/- 4.9 pmol/l) concentrations, and PRA were normal in this group of patients. There was no significant difference between the two groups of patients, however, in fasting glucose concentration and HbA1c. We conclude from these results that a reduction in plasma volume may be the major factor responsible for the induction of thirst sensation and for increased AVP secretion in NIDDM patients. The mechanism underlying a reduction in plasma volume remains unclear.

No association between MTHFR gene polymorphism and diabetic nephropathy in Japanese type II diabetic patients with proliferative diabetic retinopathy.

The development of diabetic nephropathy shows marked variation among individuals. Not only hyperglycemia, but also genetic factors may contribute to the development of diabetic nephropathy. Methylenetetrahydrofolate reductase (MTHFR) is involved in remethylation of homocysteine to methionine. Decreased activity of MTHFR which can result in hyperhomocysteinemia may lead to cerebrovascular disease and coronary artery disease. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677CT) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. In the present study, we recruited 173 of Japanese type II diabetic patients with proliferative diabetic retinopathy who would be exposed to long-term hyperglycemia, and examined the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy as microangiopathy. The frequency of the mutated allele was 43.3% in patients with nephropathy (n = 105) versus 41.9% in those without nephropathy (n = 68). The genotype frequencies were +/+, 16.2%; +/-, 54.3%; -/-, 29.5% in patients with nephropathy versus +/+, 13.2%; +/-, 57.4%; -/-, 29.4% in those without nephropathy (+ indicates the presence of the mutation). The MTHFR genotype and allele frequencies were not significantly different between patients with and without nephropathy. Therefore, we conclude that the MTHFR gene polymorphism is not associated with the development of diabetic nephropathy in Japanese type II diabetic patients.

Bisalbumin (fast and slow type) induced by human pancreatic juice.

To clarify the relationship of pancreatic juice to bisalbumin, we examined the effects of human pancreatic juice and pancreatic proteolytic enzymes on human serum albumin. Electrophoresis showed that a fast-moving band and an increased component of alpha 1-globulin appeared after incubation of serum with pancreatic juice. These components were shown to be albumins by immunofixation and immunoelectrophoresis. The alpha 1-component increased after incubation of serum with trypsin, and was confirmed as a slow-type albumin by immunoelectrophoresis. Fast-type albumin was observed after incubation of serum with chymotrypsin, and carboxypeptidases A and B. In all patients with pancreatic ascites, the fast- and slow-type albumins were seen in serum and ascitic fluid. Bisalbumins appeared in ascites at higher concentrations than in serum, and disappeared after surgical or conservative treatment. The results demonstrate that human pancreatic juice can produce fast- and slow-type albumins by proteolytic enzymes, and they are seen in patients with pancreatic ascites.