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Biomedical subjects

Y D Chen

Publications and source records attributed to Y D Chen.

At least 109 records · Page 6Linked to original sources
PubMed1992

Insulin resistance, hyperinsulinemia, and dyslipidemia in nonobese individuals with a family history of hypertension.

Various facets of glucose, insulin, and lipid metabolism were compared in 76 normal volunteers--38 with and 38 without a family history of hypertension. The two groups were comparable in terms of age, gender distribution, and degree of obesity (both generalized and abdominal). Although the plasma glucose response to oral glucose was similar in both groups, glucose-stimulated insulin concentrations were significantly greater in volunteers with a family history of hypertension (P < .001). Furthermore, the steady state plasma glucose concentration during a constant infusion of glucose, insulin and somatostatin was significantly greater in subjects with a family history of hypertension (8.1 +/- 0.6 v 6.2 +/- 0.6 mmol/L, P < .001). Since the steady-state plasma insulin levels during the infusion were similar, these results indicate that normotensive individuals with a family history of hypertension are relatively insulin resistant. Finally, plasma very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol were higher in those with a family history of hypertension, as was the ratio of total to high density lipoprotein cholesterol. Thus, normotensive individuals with a family history of high blood pressure are insulin resistant, hyperinsulinemic and dyslipidemic when compared to a matched group of healthy volunteers without a family history of hypertension.

Adult↗
PubMed1992

Glucose, insulin, and lipid metabolism in doxazosin-treated patients with hypertension.

The metabolic changes associated with doxazosin treatment of hypertension were evaluated in ten patients with mild hypertension (mean +/- SEM = 150 +/- 3/100 +/- 1 mm Hg) and a plasma triglyceride (TG) concentration > 1.50 mmol/L. The blood pressure was lower after 4 to 6 months of doxazosin treatment (mean +/- SEM = 134 +/- 4/87 +/- 1 mm Hg), which was also associated with a significantly lower plasma insulin response to a 75 g oral glucose load, and lower plasma TG and cholesterol concentrations. In addition, insulin-mediated glucose uptake was significantly greater after doxazosin treatment. These data suggest that doxazosin treatment of patients with mild hypertension is associated with changes in insulin and lipid metabolism that should decrease the risk of coronary heart disease.

Adult↗
PubMed1992

Insulin resistance and abnormal electrocardiograms in patients with high blood pressure.

Plasma glucose and insulin responses to an oral glucose challenge and fasting plasma lipid and lipoprotein concentration were compared in 25 normal individuals and 53 patients with high blood pressure. Patients with hypertension were further subdivided into two groups--normal electrocardiogram (EKG) (n = 24) or abnormal EKG (n = 29)--using the Minnesota code criteria. Patients with hypertension and an abnormal EKG had significantly higher plasma glucose and insulin concentrations following oral glucose than did the control population. Furthermore, plasma triglyceride (TG) concentration was higher and high density lipoprotein cholesterol concentration lower then normal in hypertensive patients with an abnormal EKG, and the ratio of total to HDL cholesterol was higher in this subgroup. Values for patients with high blood pressure and a normal EKG were intermediate. Insulin-mediated glucose uptake was also measured in a subset of patients with hypertension and either a normal (n = 18) or abnormal (n = 17) EKG. When these two subgroups were compared, those with high blood pressure and an abnormal EKG were significantly more insulin resistant than patients with hypertension and a normal EKG. In addition, they also had higher plasma glucose and insulin responses to oral glucose, higher fasting plasma triglyceride and cholesterol concentrations, and an increase in the ratio of total to HDL cholesterol. Thus, patients with high blood pressure have abnormalities of glucose, insulin, and lipid metabolism when compared to a nonhypertensive control group, and the magnitude of these metabolic defects is significantly greater in patients with high blood pressure who have EKG evidence of coronary heart disease.

Administration, Oral↗
PubMed1992

Improvement in metabolic risk factors for coronary heart disease associated with cilazapril treatment.

Patients with hypertension tend to be glucose intolerant, hyperinsulinemic, and dyslipedemic. Since all of these changes increase risk of coronary heart disease (CHD), it is important to know what effect antihypertensive treatment has on these variables. The current open-labelled, uncontrolled study was initiated in order to extend our understanding of these issues. This study was performed in 19 patients with hypertension who were started on an angiotensin converting enzyme (ACE)-inhibitor, cilazapril, with hydrochlorothiazide (HC) added if needed to control blood pressure. Plasma glucose and insulin responses to oral glucose and lipid concentrations were measured before, 26, and 52 weeks after starting treatment. Patients treated with either cilazapril (n = 9) or cilazapril+HC (n = 10) did not differ in terms of original (mean +/- SEM) blood pressure (159 +/- 5/101 +/- 1 v 156 +/- 4/103 +/- 2 mm Hg), age (53 +/- 2 v 54 +/- 2 years), sex distribution (5M:4F v 7M:3F), or body mass index (24.4 +/- 0.5 v 24.2 +/- 0.9 kg/m2). Blood pressure was also similar after 26 (137 +/- 4/88 +/- 1 v 133 +/- 3/90 +/- 1 mm Hg) and 52 (137 +/- 4/87 +/- 1 v 134 +/- 4/89 +/- 2 mm Hg) weeks of treatment. Plasma glucose and insulin responses decreased by 8 +/- 3% (P less than .05) and 25 +/- 9% (P less than .002), respectively, in cilazapril-treated patients, but did not change in those treated with cilazapril plus HC.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Demonstration of a relationship between white blood cell count, insulin resistance, and several risk factors for coronary heart disease in women.

In order to evaluate the relationship between peripheral white blood cell (WBC) count, insulin-mediated glucose uptake, and several risk factors for coronary heart disease (CHD), WBC, plasma glucose and insulin responses to a 75-g oral glucose challenge, fasting plasma cholesterol, high-density-lipoprotein (HDL)-cholesterol, and triglyceride concentration, and systolic and diastolic blood pressure were determined in 63 consecutive female volunteers with normal glucose tolerance. The results demonstrated the presence of statistically significant correlation coefficients between WBC count and both insulin-mediated glucose disposal (r = 0.50, P less than 0.001) and insulin response to oral glucose (r = 0.50, P less than 0.001). Furthermore, WBC count correlated with plasma glucose response to oral glucose (r = 0.48, P less than 0.001), fasting plasma triglyceride (r = 0.37, P less than 0.005) and HDL-cholesterol concentrations (r = -0.38, P less than 0.005), and systolic (r = 0.22, P less than 0.1) and diastolic (r = 0.27, P less than 0.05) blood pressure. However, the only two variables significantly correlated with WBC count in multivariate regression analysis were insulin resistance (r = 0.49, P less than 0.01) and insulin response (r = 0.35, P less than 0.05). These data indicate that WBC count is significantly correlated with changes in carbohydrate and lipoprotein metabolism and blood pressure that increase the risk of CHD. However, it appears that these relationships are secondary to resistance to insulin-mediated glucose uptake and hyperinsulinaemia.

Adult↗
PubMed1992

Effect of acute variations in dietary fat and carbohydrate intake on retinyl ester content of intestinally derived lipoproteins.

Vitamin A was administered to eight patients with noninsulin-dependent diabetes mellitus in conjunction with the two different test meals containing (as percentage of total calories) either 15% protein, 60% carbohydrate (CHO), and 25% fat or 15% protein, 40% CHO, and 45% fat. The vitamin A and test meals were given at noon (4 h after a standard breakfast), and blood was obtained hourly from noon to midnight for measurement of plasma glucose, insulin, triglyceride (TG), and cholesterol concentrations; concentrations of TG and cholesterol in Sverdberg floatation (Sf) unit above 400 and Sf 20-400 lipoproteins; retinyl ester concentration in plasma; and both Sf more than 400 and Sf 20-400 lipoproteins. The postprandial TG response in plasma, Sf more than 400 lipoproteins, and Sf 20-400 lipoproteins from noon to midnight was only slightly higher than values seen after consumption of the 60% CHO diet, which contained much less fat (25% vs. 45%) and the retinyl ester concentration was actually higher in both lipoprotein fractions after the diet containing the smallest amount of fat (60% CHO). Furthermore, the cholesterol concentration in the plasma and two lipoprotein fractions was identical after the two diets, despite the great difference in fat content. These data indicate that the acute ingestion of high CHO (60%), low fat (25%) diets by patients with noninsulin-dependent diabetes mellitus led to little or no decrease in postprandial plasma or lipoprotein TG or cholesterol concentrations and an actual increase in concentration of potentially atherogenic small chylomicron and/or chylomicron remnants.

Aged↗
PubMed1992

Combined metformin-sulfonylurea treatment of patients with noninsulin-dependent diabetes in fair to poor glycemic control.

The effect of metformin treatment was studied in 13 patients with noninsulin-dependent diabetes mellitus (NIDDM), whose fasting plasma glucose concentration was greater than 10 mmol/L with maximal sulfonylurea doses. Patients were studied before and 3 months after receiving 2.5 g/day metformin. The fasting plasma glucose concentration (12.4 +/- 0.8 vs. 8.8 +/- 0.7 mmol/L), mean hourly postprandial plasma glucose concentration from 0800-1600 h (14.0 +/- 1 vs. 9.4 +/- 0.9 mmol/L), and glycosylated hemoglobin level (12.3 +/- 0.6% vs. 9.0 +/- 0.6%) were all significantly (P less than 0.005-0.001) lower after the administration of metformin. The improvement in glycemic control was associated with a 24% increase (P less than 0.05) in insulin-stimulated glucose uptake during glucose clamp studies and a 16% decrease in basal hepatic glucose production (P less than 0.05). Mean hourly concentrations of plasma insulin (411 +/- 73 vs. 364 +/- 73 pmol/L) and FFA concentrations (440 +/- 31 vs. 390 +/- 40 mumol/L) were also lower after 3 months of metformin treatment. However, neither insulin binding nor insulin internalization by isolated monocytes changed in response to metformin. Finally, plasma triglyceride, very low density lipoprotein triglyceride, and very low density lipoprotein cholesterol were significantly decreased (P less than 0.01-0.001), and high density lipoprotein cholesterol was significantly increased (P less than 0.001) after metformin treatment. Thus, the addition of metformin to sulfonylurea-treated patients with NIDDM not in good glycemic control significantly lowered fasting and postprandial plasma glucose concentrations, presumably due to the combination of enhanced glucose uptake and decreased hepatic glucose production. Since the dyslipidemia present in these patients also improved, the results suggest that metformin may be of significant clinical utility in patients with NIDDM not well controlled with sulfonylurea compounds.

Blood Glucose↗
PubMed1992

[Studies on the establishment of malarial animal model of short-term relapse. I. Asynchronous growth of exoerythrocytic schizonts of Plasmodium cynomolgi].

A monkey was infected with sporozoites of Plasmodium cynomolgi from Vietnam. Parasitemia was detected on the 8th day with a starting density of 17/100 white blood cells. 22 hours after that time, many EE schizonts appeared with an average density of 3.74 +/- 0.66 per mm3 hepatic tissue in liver biopsy specimens from the monkey. Most of the EE schizonts were immature and grew at an uneven rate, having an average diameter of 34.22 +/- 7.28 microns but some of them even remained 15.75 +/- 2.47 microns in diameter similar to the EE schizonts on the 6th day. The results showed that the EE schizonts of Plasmodium cynomologi were asynchronous in growth. The authors suggest that the release of merozoites from liver might be a successive process for many times, and not to be completed at a time.

Animals↗
PubMed1992

[The expression of TGF beta-related mRNAs in the early development of Xenopus].

Using porcine TGF beta 1-cDNA probe, we found that three TGF beta-related mRNAs (4.2 kb, 3.2 kb and 2.3 kb) were detected in blastula (Stg. 7/8). The 4.2 kb and 3.2 kb mRNAs were very highly expressed in the blastula (Fig. 3). However, we could hardly detect them in embryos of cleavage, gestrula and neurula stages. On the other hand, the 2.3 kb mRNA could be identified in embryos of cleavage stages, blastula, gastrula and neurula and the quantity was rather stable. Comparing the quantities of TGF beta-related mRNAs in different parts of blastula, that is, animal half or vegetal half and dorsal or ventral half, we found that the transcripts were enriched in the vegetal hemisphere (Fig. 6). But no obvious difference between dorsal and ventral halves could be detected (Fig. 7).

Animals↗
PubMed1991

Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration.

OBJECTIVE: To define the relationship, if any, between insulin-mediated glucose disposal and serum uric acid. DESIGN: Cross-sectional study of healthy volunteers. SETTING: General Clinical Research Center, Stanford (Calif) University Medical Center. PARTICIPANTS: Thirty-six presumably healthy individuals, nondiabetic, without a history of gout. MEASUREMENTS: Obesity (overall and regional), plasma glucose and insulin responses to a 75-g oral glucose load, fasting uric acid concentrations, plasma triglyceride and high-density lipoprotein-cholesterol concentrations, systolic and diastolic blood pressure, insulin-mediated glucose disposal, and urinary uric acid clearance. RESULTS: Magnitude of insulin resistance and serum uric acid concentration were significantly related (r = .69; P less than .001), and the relationship persisted when differences in age, sex, overall obesity, and abdominal obesity were taken into account (r = .57; P less than .001). Insulin resistance was also inversely related to urinary uric acid clearance (r = -.49; P less than .002), and, in addition, urinary uric acid clearance was inversely related to serum uric acid concentration (r = -.61; P less than .001). CONCLUSIONS: Urinary uric acid clearance appears to decrease in proportion to increases in insulin resistance in normal volunteers, leading to an increase in serum uric acid concentration. Thus, it appears that modulation of serum uric concentration by insulin resistance is exerted at the level of the kidney.

Adult↗
PubMed1991

Comparison of the effects of atenolol and nifedipine on glucose, insulin, and lipid metabolism in patients with hypertension.

Various aspects of carbohydrate and lipid metabolism have been studied in two groups of patients with mild hypertension before and after four months of treatment with either nifedipine (n = 12) or atenolol (n = 12). Mean (+/- SEM) blood pressure fell to the same degree following treatment with either nifedipine (147 +/- 3/98 +/- 2 to 134 +/- 2/85 +/- 2 mm Hg) or atenolol (149 +/- 3/99 +/- 2 to 135 +/- 2/86 +/- 3 mm Hg). Circulating plasma glucose, insulin, and triglyceride concentrations were measured at hourly intervals from 8:00 AM to 4:00 PM, before and after breakfast (8:00 AM), and at lunch time (noon). The response to treatment was different in the two groups. Specifically, plasma glucose concentration were unchanged and insulin concentrations were higher in association with atenolol treatment. In contrast, nifedipine-treated patients had similar plasma insulin, but lower plasma glucose and triglyceride concentrations after four months of therapy. The changes in day-long plasma glucose and insulin responses suggested that resistance to insulin-stimulated glucose uptake had increased in association with atenolol treatment and decreased following nifedipine. This conclusion was supported in that measurement of insulin-stimulated glucose disposal showed a decrease in atenolol-treated patients and an increase in nifedipine-treated patients. Finally, plasma lipoprotein cholesterol concentrations did not change following atenolol therapy, whereas plasma high density lipoprotein cholesterol increased in association with nifedipine administration. These data show that changes in carbohydrate and lipid metabolism observed with treatment of mild hypertension can vary significantly as a function of the drug used, despite similar beneficial effects on blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Atenolol↗
PubMed1991

Changes in carbohydrate metabolism in association with glipizide treatment of type 2 diabetes.

Nineteen patients with Type 2 diabetes were treated with glipizide for 2.5-6 months, and measurements made of metabolic variables before and after glipizide treatment. For purposes of analysis, the glipizide associated decrease in fasting plasma glucose concentration was used to divide patients into 'good' responders (decrease of 4.0 mmol l-1 or more, n = 9) or 'fair' responders (decrease of 3.0 mmol l-1 or less, n = 10). Good responders had a significantly greater fall in their mean (+/- SE) hourly plasma glucose (6.3 +/- 0.6 vs 2.7 +/- 0.3 mmol l-1, p less than 0.001) and NEFA (164 +/- 40 vs 60 +/- 37 mumol l-1, p less than 0.05) concentrations from 0800 to 1600 h in response to meals (0800 and 1200 h) than did the fair responders. However, the increase in hourly plasma insulin concentration following glipizide treatment was the same in the good (323 +/- 103 to 413 +/- 124 pmol l-1) and fair (276 +/- 42 to 345 +/- 43 pmol l-1) responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1991

Regulation of non-esterified fatty acid and glycerol concentration by insulin in normal individuals and patients with type 2 diabetes.

Plasma glycerol and non-esterified fatty acid (NEFA) concentrations were determined in the basal state and in response to physiological hyperinsulinaemia in 30 non-obese individuals, 15 with Type 2 diabetes and 15 with normal glucose tolerance. Patients with Type 2 diabetes had higher basal concentrations of both glycerol (81 +/- 7 (+/- SE) vs 61 +/- 7 mumol l-1, p less than 0.05) and NEFA (842 +/- 40 vs 630 +/- 46 mumol l-1, p less than 0.002). Plasma NEFA and glycerol concentrations fell in both groups when steady-state plasma insulin concentrations were raised to approximately 450 pmol l-1 by an infusion of exogenous insulin, but plasma concentrations of glycerol (28 +/- 3 vs 13 +/- 3 mumol l-1, p less than 0.002) and NEFA (186 +/- 15 vs 109 +/- 14 mumol l-1, p less than 0.001) were still higher in patients with Type 2 diabetes. Percentage decrease in glycerol from basal levels in response to insulin was significantly less in patients with Type 2 diabetes than in control subjects (64 +/- 3 vs 80 +/- 3%, p less than 0.005); percentage decrease in plasma NEFA concentration was similar in the two groups (78 +/- 3 vs 80 +/- 4%). These results suggest that both plasma glycerol and NEFA concentrations are higher than normal in patients with Type 2 diabetes when measured at the same insulin concentration, both under basal conditions and in response to physiological hyperinsulinaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1991

High density lipoprotein turnover in patients with hypertension.

Although hyperinsulinemia and decreased high density lipoprotein cholesterol concentration can occur in patients with hypertension, there is no information available concerning the dynamic state of high density lipoprotein metabolism. To address this issue, we quantified high density lipoprotein turnover in 12 patients with mild hypertension and 11 matched subjects with normal blood pressure. Patients with high blood pressure had lower high density lipoprotein cholesterol concentrations. Fractional catabolic rates of 125I-apolipoprotein AI (apoAI)/high density lipoprotein were faster in patients with hypertension (0.36 +/- 0.02 versus 0.26 +/- 0.02 l/day, p less than 0.001). Total synthetic rates of apoAI were also significantly greater in patients with high blood pressure (17.4 +/- 1.1 versus 13.2 +/- 0.6 mg/kg/day, p less than 0.001). Although significant correlation was observed between blood pressure and fractional catabolic rate of 125I-apoAI/high density lipoprotein in the experimental population (r = 0.52, p less than 0.01), no relation was found when patients with normal blood pressure or hypertension were considered separately. However, a highly significant positive correlation was found between 125I-apoAI/high density lipoprotein fractional catabolic rate and insulin concentration in the entire population (r = 0.72, p less than 0.001). In conclusion, the patients with mild hypertension studied were hyperinsulinemic, had a faster fractional catabolic rate of 125I-apoAI/high density lipoprotein, and a lower high density lipoprotein-cholesterol concentration. It is suggested that the changes seen in high density lipoprotein-cholesterol concentration and 125I-apoAI/high density lipoprotein fractional catabolic rates were secondary to the hyperinsulinemia and not due to the high blood pressure per se.

Adult↗
PubMed1991

Effect of gemfibrozil treatment in sulfonylurea-treated patients with noninsulin-dependent diabetes mellitus.

This study was initiated to 1) assess gemfibrozil's ability to lower plasma triglyceride (TG) concentration in patients with NIDDM, and 2) determine whether this effect was associated with any changes in glycemic control. Measurements were made of mean hourly plasma glucose, insulin, TG, and FFA concentrations from 1200-1600 h in response to a test meal; hepatic glucose production (HGP); insulin-stimulated glucose uptake during a hyperinsulinemic glucose clamp study (MCR); and fasting plasma lipoprotein TG and cholesterol concentrations in 12 patients with NIDDM before and 3 months after gemfibrozil treatment. Although ambient plasma TG and FFA concentrations fell significantly, plasma glucose, insulin, HGP, concentrations fell significantly, plasma glucose, insulin, HGP, and glucose MCR did not change. However, when patients were divided into two groups, those with fasting plasma glucose levels above 9 mmol/L (fair control) and those with levels below 9 mmol/L (good control), a different phenomenon was observed. Patients in fair control had significant decreases in mean hourly plasma concentrations of glucose (15.1 +/- 1.7 to 12.6 +/- 0.9 mmol/L; P less than 0.001), insulin (523 +/- 59 to 471 +/- 75 pmol/L; P less than 0.001), FFA (652 +/- 150 to 504 +/- 76 mumol/L), and HGP (9.5 0.4 to 8.1 +/- 0.4 mumol/kg.min; P less than 0.005), and an increase in glucose MCR (2.63 +/- 0.49 to 3.72 +/- 0.54 mL/kg.min; P less than 0.07) in association with a fall in TG from 6.9 +/- 1.3 to 3.5 +/- 0.9 mmol/L (P less than 0.001). Although fasting low density lipoprotein cholesterol increased (1.8 +/- 0.2 to 2.7 +/- 0.2 mmol/L; P less than 0.05), the ratio of total to high density lipoprotein cholesterol decreased (6.84 +/- 0.88 to 5.80 +/- 1.05; P less than 0.02). Despite a significant fall in mean hourly TG concentration (4.6 +/- 0.7 to 3.8 +/- 0.7 mmol/L; P less than 0.001), neither insulin, FFA, HGP, nor glucose MCR changed in patients in good control. Furthermore, the mean hourly plasma glucose concentration increased from 9.2 +/- 0.7 to 11.7 +/- 1.4 mmol/L (P less than 0.001). Low density lipoprotein cholesterol also increased in this group (1.9 +/- 0.2 to 2.7 +/- 0.2 mmol/L; P less than 0.02), but, as before, the ratio of total to high density lipoprotein cholesterol decreased (8.15 +/- 1.93 to 6.36 +/- 1.03; P less than 0.02).

Blood Glucose↗
PubMed1991

Production of inhibitor of insulin-receptor tyrosine kinase in fibroblasts from patient with insulin resistance and NIDDM.

Although non-insulin-dependent diabetes mellitus (NIDDM) is associated with defects in insulin action, the molecular basis of this resistance is unknown. We studied fibroblasts from a markedly insulin-resistant patient with NIDDM but without acanthosis nigricans. Her fibroblasts were resistant to insulin when alpha-aminoisobutyric acid uptake was measured. Fibroblasts from this patient demonstrated normal insulin-receptor content as measured by both insulin-receptor radioimmunoassay and by Scatchard analysis. However, when compared with nondiabetic control subjects, insulin-receptor kinase assays of wheat-germ-purified receptors prepared from her fibroblasts showed very low basal and no insulin-stimulated tyrosine kinase activity. The insulin receptor was then removed from the wheat-germ fraction by monoclonal antibody affinity chromatography. This insulin-receptor-deficient fraction inhibited both basal and insulin-stimulated tyrosine kinase activity of highly purified insulin receptors. When the specificity of this inhibition was tested, less inhibition was seen with insulinlike growth factor I-receptor tyrosine kinase, and even less inhibition was seen with the proto-oncogene p60c-src tyrosine kinase. Thus, these studies indicate that fibroblasts from an insulin-resistant patient with NIDDM produce a relatively specific glycoprotein inhibitor of insulin-receptor tyrosine kinase. Therefore, these studies raise the possibility that this inhibitor may play an important role in the insulin resistance seen in this patient.

Adult↗
PubMed1990

A general secular equation for cooperative binding of n-mer ligands to a one-dimensional lattice.

The binding of n-mer ligands to a one-dimensional lattice involving many ligand species and complex multiple-binding mechanisms is studied. We show that, when derived using the sequence-generating function method of Lifson, the secular equation of any binding system with a finite number of "elementary units" can be expressed in a matrix determinant form that is very symmetric and easy to construct. In other words, for any binding system whose elementary units are known, the secular equation of the system can be obtained readily without going through the formal derivation of the equation. We also show that the "determinant" secular equation obtained using the present procedure can be employed directly to the calculation of binding isotherms.

Algorithms↗