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Biomedical subjects

A M Acosta

Publications and source records attributed to A M Acosta.

At least 19 recordsLinked to original sources

A neuroprosthesis for high tetraplegia.

BACKGROUND: This case report describes a neuroprosthesis that restored shoulder and elbow function in a 23-year-old man with chronic C3 complete tetraplegia. Before implementation of the neuroprosthesis, electrodiagnostic testing revealed denervation from C5 to T1, with the greatest degree of denervation in the C8 and T1 myotomes. Thirteen percutaneous intramuscular electrodes were implanted into muscles acting on the shoulder and elbow of one upper limb. Before functional testing, the subject underwent a conditioning regimen to maximize the strength and endurance of the implanted muscles. RESULTS: After completion of the 8-week exercise regimen, stimulated active range of motion against gravity included 60 degrees of shoulder abduction, 45 degrees of shoulder flexion, 10 degrees of shoulder external rotation with the shoulder passively abducted to 90 degrees, and 110 degrees of elbow flexion. Stimulated elbow extension lacked 20 degrees of full extension with gravity eliminated. After system setup, the subject was able to pick up mashed potatoes on a plate with a utensil and bring them to his mouth using the neuroprosthesis and a balanced forearm orthosis. A switch mounted on the headrest of the subject's wheelchair and a position sensor mounted on the contralateral shoulder allowed the subject to control movement of his upper limb.

Activities of Daily Living↗

Three-dimensional shoulder kinematics in individuals with C5-C6 spinal cord injury.

The shoulder kinematics of five able-bodied subjects and those of five arms in three subjects with spinal cord injuries at C5 or C6 levels were measured as the subjects elevated their arms in three different planes: coronal, scapular and sagittal. The range of humeral elevation was significantly reduced in all spinal cord injury (SCI) subjects relative to able-bodied subjects. Over this restricted range of humeral motion, the scapula of SCI subjects tended to be medially rotated, relative to able-bodied subjects, and the protraction and spinal tilt angles of the scapula of the SCI subjects indicated scapular winging. These results are consistent with paralysis or at least with significant weakness of the serratus anterior muscle. If further study confirms this hypothesis, functional neuromuscular stimulation of the serratus anterior muscle via a nerve cuff electrode may be an effective intervention for improving shoulder function in C5-C6 SCI.

Biomechanical Phenomena↗

APC stimulated by CpG oligodeoxynucleotide enhance activation of MHC class I-restricted T cells.

Oligonucleotides containing unmethylated CpG motifs (cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG ODN)) are potent immunostimulatory agents capable of enhancing the Ag-specific Th1 response when used as immune adjuvants. We evaluated the cellular mechanisms responsible for this effect. Development of a CTL response was enhanced when mice were immunized with peptide-pulsed dendritic cells (DCs) treated with CpG ODN. However, in vitro, CpG ODN had no direct effect on highly purified T cells. In vitro, CpG ODN treatment of peptide- or protein-pulsed DCs enhanced the ability of the DCs to activate class I-restricted T cells. The presence of helper T cells enhanced this effect, indicating that treatment with CpG ODN does not obviate the role of T cell help. The enhanced ability of CpG ODN-treated DCs to activate T cells was present but blunted when DCs derived from IL-12 knockout mice were used. Fixation of Ag-pulsed, CpG ODN-treated DCs limited their ability to activate T cells. In contrast, fixation had little effect on DC activation of T cells when DCs were not exposed to CpG ODN. This indicates that production of soluble factors by DCs stimulated with CpG ODN plays a particularly important role in their ability to activate class I-restricted T cells. We conclude that CpG ODN enhances the development of a cellular immune response by stimulating APCs such as DCs, to produce IL-12 and other soluble factors.

Adjuvants, Immunologic↗

A robotic manipulator for the characterization of two-dimensional dynamic stiffness using stochastic displacement perturbations.

Experimental techniques for estimating the two-dimensional dynamic stiffness of the human arm over a wide range of conditions have been developed. A robotic manipulator has been developed to create loads against which subjects perform various tasks and also to impose perturbations onto the endpoint of the arm to allow estimation of its mechanical properties. The manipulator can produce static endpoint forces exceeding 220 N in any direction in its plane of motion, and this plane can be vertically translated and tilted over wide ranges to study arm dynamic stiffness in many functionally relevant planes. It can impose stochastic position and force perturbations whose bandwidth exceeds that of the arm. These random perturbations avoid undesirable volitional reactions and allow the efficient estimation of stiffness dynamics using experimental trials of short duration. The ability of this manipulator to characterize inertial-viscoelastic systems was tested using several two-dimensional physical systems whose properties were independently characterized. The endpoint dynamic stiffness properties of a human arm were estimated as an example of the use of the manipulator in studying upper limb mechanical properties. The system properties characterized by these methods will be useful in probing normal neural arm control strategies and in developing rehabilitation interventions to improve arm movements in disabled individuals.

Arm↗

(AC)23 [Z-2] polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics.

A recent case-control study suggests that the allele (AC)23 of a variable number tandem repeat (VNTR) associated to the aldose reductase (ALR2) gene could be related to early retinopathy in Type 2 diabetics. By means of a longitudinal-retrospective study, we aimed to seek for a relationship between the rate of progression of retinopathy and the (AC)23 allele of the VNTR associated to the ALR2 gene. A random sample was obtained of 27 Type 2 diabetics (aged 68.1 +/- 10.6 years, diabetes duration = 20.7 +/- 4.8 years, mean HbA1 = 10.6 +/- 1.6%). The mean HbA1 was the arithmetic average of 2.2 measurements per patient per year of total glycosilated hemoglobin (Gabbay method, normal range: 4.2-7.5%). Retinopathy was graded by an Ophthalmologist in a scale from zero to four score points. The genotype of the (AC), VNTR was determined by 32P-PCR plus sequenciation in a Perkin-Elmer laser device. The Mann-Whitney test and either chi2 or Fisher's exact test were used. A P < 0.05 was considered as statistically significant. The retinopathy progression rate (RPR, points x year(-1)) was calculated by dividing the increment of retinopathy score (delta Retinopathy Score, [points]), by the duration of the follow up [years]. The 12 diabetics having the (AC)23 allele had a mean RPR 8.9 times higher (0.40 +/- 0.61 points x year(-1)) than the 15 patients who had alleles other than (AC)23 (0.045 +/- 0.099 points x year(-1), P = 0.037). Both groups were similar with respect to: mean HbA1 (10.5 +/- 1.4 and 10.7 +/- 1.7%, P = 0.95), age at diagnosis (48.5 +/- 6.3 and 46.3 +/- 14.0 years, P = 0.81), diabetes' duration (21.3 +/- 4.7 and 20.2 +/- 4.9 years, P = 0.41) and serum creatinine (0.89 +/- 0.2 and 1.13 +/- 0.5 mg dl(-1), P = 0.35). We concluded that, in Type-2 diabetics having similar glycemic control, the (AC)23 allele of the VNTR associated to the ALR2 gene, is associated to a 8.9 times faster progression of retinopathy than in patients who have other alleles.

Age of Onset↗

Multiple-input, multiple-output system identification for characterization of limb stiffness dynamics.

This study presents time-domain and frequency-domain, multiple-input, multiple-output (MIMO) linear system identification techniques that can be used to estimate the dynamic endpoint stiffness of a multijoint limb. The stiffness of a joint or limb arises from a number of physiological mechanisms and is thought to play a fundamental role in the control of posture and movement. Estimates of endpoint stiffness can therefore be used to characterize its modulation during physiological tasks and may provide insight into how the nervous system normally controls motor behavior. Previous MIMO stiffness estimates have focused upon the static stiffness components only or assumed simple parametric models with elastic, viscous, and inertial components. The method presented here captures the full stiffness dynamics during a relatively short experimental trial while assuming only that the system is linear for small perturbations. Simulation studies were performed to investigate the performance of this approach under typical experimental conditions. It was found that a linear MIMO description of endpoint stiffness dynamics was sufficient to describe the displacement responses to small stochastic force perturbations. Distortion of these linear estimates by nonlinear centripetal and Coriolis forces was virtually undetectable for these perturbations. The system identification techniques were also found to be robust in the presence of significant output measurement noise and input coupling. These results indicate that the approach described here will allow the estimation of endpoint stiffness dynamics in an experimentally efficient manner with minimal assumptions about the specific form of these properties.

Algorithms↗

[Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetics].

BACKGROUND: Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. AIM: To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. PATIENTS AND METHODS: A random sample of 27 NIDDM, aged 68.1 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glycosilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5' end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. RESULTS: Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p = 0.047). Both groups had similar glycosilated hemoglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. CONCLUSIONS: Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5' end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate.

Age of Onset↗

[Prevalence of islet cell antibodies among 1021 relatives of type 1 diabetics].

BACKGROUND: An immunological damage of beta cells in the islets of Langerhans, plays a role in the pathogenesis of type 1 diabetes. Recently, the identification of individuals in pre clinical phase and with high risk of developing type 1 diabetes, has become possible by means of the detection of immune markers such as islet cell antibodies (ICA) and the measurement of first phase response of insulin (FPRI). SUBJECTS AND METHODS: We studied 1,021 first degree relatives of type 1 diabetics, aged 4 to 35 years. ICA were measured using poly-IgG peroxidase in sections of human pancreas. In those subjects with positive ICA and normal oral glucose tolerance test, the FPRI was measured. FPRI was defined as the sum of insulinemias at minutes 1 and 3 after a three minutes 0.5 g/kg glucose load. RESULTS: Thirty subjects were ICA (+), defined as having more than 20 juvenile diabetes foundation units (prevalence of 2.9%). No differences in age, sex and closeness of familial relationship was found between ICA (+) and ICA (-) individuals. FPRI was measured in 24 subjects with normal oral glucose tolerance test and was normal in five. Seventeen subjects had a decreased response (between percentiles 1 and 5) and two had a response below percentile 1. No relationship between ICA levels and FPRI was found. CONCLUSIONS: The early detection of populations at risk of developing type 1 diabetes should be regarded as an important tool to better understand the natural history of the disease and to develop preventive programs in the future.

Adolescent↗

[Transcranial cytokine gradient and intestinal permeability in acute severe brain injury].

BACKGROUND: Acute brain injury is associated with a bimodal hypermetabolic state probably caused by cytokine secretion and high hormone and catecholamine concentrations. In a first stage, the brain would produce these substances and afterwards, another production source, most probably the splanchnic territory, would perpetuate the hypermetabolic state. AIM: To investigate the cytokine production source and to assess intestinal permeability in acute brain injury in the absence of cerebral ischemia and systemic oxygen deficit. PATIENTS AND METHODS: Arterial systemic and cerebral venous bulbar interleukin 1 beta and interleukin 6 levels were measured during the first seven days of evolution in 15 patients with acute brain injury. Serum lactate, the oxygen/lactate ratio, gastric intramucosal pH and intestinal permeability using the lactulose/mannitol test were also assessed in the same period. RESULTS: High arterial and venous interleukin 1 beta and interleukin 6 levels were detected. A positive gradient for interleukin 6 levels was detected throughout the study period with normal intramucosal pH, lactate and oxygen/lactate ratio. There was also an early impairment of intestinal permeability in these patients. CONCLUSIONS: High arterial and venous cytokine concentrations were detected in patients with acute brain injury. The positive gradient for interleukin 6 suggests a brain origin for this cytokine. Intestinal permeability is also altered in these patients.

Adult↗

Sex differences in estrogenic regulation of preproenkephalin mRNA levels in the medial preoptic area of prepubertal rats.

Opioids have been implicated in sexual differentiation of the brain and in the regulation of reproductive behavior and endocrinology of mammals. Previous studies have indicated that estrogen administration in adults regulates preproenkephalin MRNA levels in several hypothalamic brain nuclei. We have determined preproenkephalin mRNA levels in estrogen-treated juvenile male and female rats to investigate the developmental pattern of estrogenic regulation of enkephalinergic neurons in the medial preoptic area. Rats were treated with estradiol benzoate (20 microgram/kg/day) or oil from day 21 to 23. Sections of the medial preoptic area (mPOA) were studied by in situ hybridization histochemistry at the single cell level and quantified with the assistance of an image analysis system. Our data indicate that males contain higher levels of preproenkephalin mRNA per neuron than females. In addition, our results indicate that estrogen causes an upward shift in the amount of mRNA expressed per cell, females demonstrating a greater response to estrogen than males. An increase in soma cell area following estrogen treatment was observed only in female mPOA enkephalinergic neurons. Taken together, these results indicate a sex difference in total preproenkephalin levels and in estrogenic regulation of preproenkephalin mRNA in the POA of juvenile rats. These results are discussed in relation to the differential role opioids may play in male and female reproductive physiology.

Animals↗

[Diabetic neuropathy: thermal sensation and metabolic control in non-insulin-dependent diabetics].

BACKGROUND: The early detection of peripheral neuropathy in diabetics is important since it is the main risk factor for lower limb trophic lesions in diabetics. AIM: To assess the relationship between feet thermal sensation threshold and metabolic control in ambulatory non-insulin-dependent diabetics. PATIENTS AND METHODS: A random sample of 34 non-insulin-dependent diabetics followed for more than five years in a special clinic, out of 368 patients, was selected. Warmth sensation thresholds were measured in the dorsum of both feet using a MSTP-III thermostimulator. The average value of all glycosylated hemoglobins obtained during the 9.7 +/- 5.3 years of follow up for each patient was calculated. A multiple stepwise regression analysis was performed between thermal sensation as the dependent variable and glycosylated hemoglobin, fasting blood glucose, age and diabetes duration. RESULTS: The regression model disclosed glycosylated hemoglobin as the only independent predictor of warmth sensation threshold (partial r = 0.385; p = 0.043). Fifteen diabetic patients with good metabolic control, defined as those with a mean glycosylated hemoglobin of less than 9.5%, had a warmth sensation threshold of 35.6 +/- 3.7 degrees C, whereas 19 diabetics with a had control (glycosylated hemoglobin > or = 9.5%) had a threshold of 39 +/- 3.8 degrees C (p = 0.017). CONCLUSIONS: In this group of diabetics, there is a relationship between the severity of distal polyneuropathy and the metabolic control, assessed with glycosylated hemoglobin levels.

Aged↗

Measurement of isometric elbow and shoulder moments: position-dependent strength of posterior deltoid-to-triceps muscle tendon transfer in tetraplegia.

This report describes an apparatus which has been developed to measure several isometric elbow and shoulder forces and moments simultaneously and also allows this characterization to be performed across a range of shoulder and elbow joint angles in a horizontal plane. This apparatus was used to characterize the elbow extension strength in individuals with tetraplegia resulting from cervical level spinal cord injury. In all of these individuals, voluntary elbow extension was provided exclusively by the posterior deltoid muscle, which had previously been surgically transferred to the tendon of the paralyzed triceps muscle. Elbow extension is essential for many daily activities, such as reaching above shoulder level and pushing objects away from the body; the widely used posterior deltoid-to-triceps muscle tendon transfer surgery restores some degree of voluntary control to this important function. The apparatus contained a six-axis force-moment transducer to which the arm of each subject was attached. The six outputs of the transducer were transformed to correspond to physiological elbow and shoulder moments and forces. A customized table allowed the shoulder and elbow angles of the subject to be varied over a wide range in a horizontal plane so that the effects of posterior deltoid muscle length could be characterized over the likely functional range of the subject within this plane. It was found that elbow extension strength varied widely across subjects with C5 or C6 tetraplegia, from quite weak to strong enough to propel a manual wheelchair. Furthermore, the elbow extension strength of most subjects showed a strong dependence on both elbow and shoulder angles. Elbow extension was typically weak when the upper arm was elevated to shoulder level at the side, which unfortunately corresponds to the position often adopted by these individuals due to shoulder weakness.

Elbow Joint↗

[Indicators of atherosclerosis risk. Evaluation with coronary angiography in non diabetic men with total cholesterol levels equal to or below 240 mg/dl].

We studied 90 male non diabetic patients aged between 40 and 65 years old with a total cholesterol of less than 240 mg/dl and not receiving cholesterol reducing drugs, that were subjected to elective coronary arteriography. Weight, height, blood pressure and smoking habits were recorded and a fasting blood sample was drawn to measure total and HDL cholesterol, triglycerides, apoproteins A1 and B, Lipoprotein(a) and plasma cholesteryl ester transfer activity. Arteriography disclosed coronary lesions in 54 patients. Compared to patients without lesions, the former had lower HDL cholesterol (34 +/- 9.8 vs 40.2 +/- 11.6 mg/dl) and higher total cholesterol/HDL cholesterol and apoB/apoA1 ratios. No differences were found for lipoprotein(a) and plasma cholesteryl ester transfer activity. Univariate analysis showed that low HDL cholesterol had the best predictive capacity for atherosclerosis.

Adult↗

[Immunologic and insulin secretion markers in non insulin dependent diabetic patients with secondary failure to oral hypoglycemic drugs].

BACKGROUND: The pathogenesis of secondary failure to hypoglycemic agents is heterogeneous. Some patients are true insulin dependent diabetics with a slow autoimmune disease suggested by their positive islet cell antibodies. Others, have an increased insulin resistance. AIM: To assess the frequency of positive islet cell antibodies in diabetic patients with secondary failure to oral hypoglycemic agents. PATIENTS AND METHODS: Thirty one diabetics, 16 with recent (less than six months) secondary failure and 15 with metabolically stable non insulin dependent diabetes were studied. All patients were older than 25 years old and had a body mass index of less than 30 kg/m2. C peptide levels before and at 5, 15 and 30 min after IV glucagon, islet cell antibodies using the Poly Human IgG peroxidase method and insulin sensitivity and secretion (estimated by the Homeostasis Model Assessment) were measured. RESULTS: Patients with secondary failure had lower C peptide levels, compared to subjects with stable diabetes (basal: 1.5 +/- 0.2 and 2.8 +/- 0.2 ng/ml; 5 min: 2.4 +/- 0.3 and 5.5 +/- 0.5 ng/ml; 15 min: 1.9 +/- 0.3 and 4.0 +/- 0.6 ng/ml; 30 min: 1.6 +/- 0.3 and 3.4 +/- 0.5 ng/ml). Beta cell activity was 20.6 +/- 4.3% in patients with secondary failure and 92.2 +/- 9% in stable diabetics (p < 0.01). Insulin sensitivity was similar in both groups (48.6 +/- 6 and 42.8 +/- 3.5% respectively). Three patients with secondary failure and none with stable diabetes had positive islet cell antibodies. When comparing patients with secondary failure and positive antibodies and subjects with secondary failure and negative antibodies, the former had non significantly lower age, BMI and C peptide levels. CONCLUSIONS: Some diabetic patients with secondary failure have positive islet cell antibodies. They should be measured in these patients to start insulin treatment precociously.

Administration, Oral↗

[Variability of measured energy expenditure in patients with acute pancreatitis: is it possible to obtain a reliable pathology factor for these cases?].

Energy expenditure was measured in 55 patients with acute pancreatitis, during variable periods ranging from 1 to 5 weeks and it was compared with estimated energy expenditure according to Harris Benedict equations. Patients with severe pancreatitis had similar measured and measured/estimated energy expenditure rations, compared to those with mild pancreatitis (1678 +/- 349.6 kcal/day and 1.1 +/- 0.19 vs 1632 +/- 383 kcal/day and 1.06 +/- 0.19). There was a high dispersion of measured/estimated rations (0.67 - 1.7) that precluded the calculation of a reliable energy expenditure correction factor for this disease. It is concluded that energy expenditure must be measured and not estimated, when planning an adequate nutritional support in patients with acute pancreatitis.

Acute Disease↗

[Non-insulin-dependent diabetics with secondary failure: insulin therapy at bedtime combined with glibenclamide].

Secondary failure and the requirement is common in patients with non-insulin dependent diabetes mellitus. The combination of sulfonylureas with NPH insulin at bedtime has been proposed to avoid high doses of insulin. We treated 18 patients (2 men, age range 47-76 yr) non respondent to diet and glibenclamide, combining NPH insulin in an average dose of 0.3 +/- 0.03 U/kg BW at bedtime for 6 months. Fasting serum glucose improved from 256 +/- 11 to 132 +/- 6 mg/dl and HbA1C from 13.6 +/- 0.4 to 9.9 +/- 0.2%. Four patients achieved a good control (defined as a HbA1C < 9), 9 a fair control (HbA1C 9.1-10) and 5 persisted with a bad control (HbA1C > 10). Well controlled patients were younger, had a shorter duration of diabetes and had a non significantly higher body mass index. Fasting serum insulin and C peptide levels achieved after glucagon injection were not predictors of the metabolic response to combined therapy. Tolerance to treatment was good, without changes in blood pressure or serum lipids and with a low incidence of hypoglycemia. There was a mean increase of 3.6 kg in body weight. After 6 months of therapy, maximum achieved C peptide values after glucagon increased from 3.3 +/- 0.3 to 4.5 +/- 0.4 ng/ml. It is concluded that combined glibenclamide and NPH insulin at bedtime is useful to treat secondary failure in non-insulin dependent diabetic patients, but their response in variable and non dependent on their beta insular secretion.

Aged↗

[Dyslipidemic patients with coronary cardiopathy. Effect of different doses of OMEGA-3 fatty acids on serum lipids and lipoproteins].

Twenty one male patients aged 35 to 70 years, with coronary artery disease and dislipidemia refractory to dietary treatment, were assigned to three parallel groups of 7 individuals each that received a supplemental dose of 2, 4 and 6 g/day of omega-3 fatty acids during 60 days. After a 30 days wash-out period and 60 of supplementation, subjects were weighed, a dietary survey was performed, serum levels of total cholesterol and triglycerides, the lipid content of serum lipoproteins and the content of EPA+DHA in plasma phospholipids were measured. A dose dependent increase in EPA+DHA content of phospholipids and no changes in weight or nutrient intake were observed during the supplementation period. With the 6 g dose, a significant reduction in total cholesterol, with a reduction in VLDL and increase in LDL cholesterol and a decline in VLDL triglycerides was observed. With the 4 g dose a reduction in total cholesterol at the expense of VLDL and HDL cholesterol and a reduction in VLDL triglycerides but no changes in total triglycerides was observed. No changes in serum lipids were observed with 2 g dose. In patients with type IIA hyperlipidemia, a significant positive correlation was observed between DHA+EPA content of plasma phospholipids and LDL cholesterol, this correlation was not observed in patients with IIB or IV phenotypes. It is concluded that omega-3 fatty acids are ineffective as the only treatment for dislipidemias refractory to diet.

Adult↗

[The effect of a peripheral androgenic blockade on plasma lipoproteins in hirsutism patients].

We studied the effect of flutamide, a peripheral androgenic blocking agent, 500 mg daily for 28 days in 7 non ovulating patients with hirsutism. Total and HDL cholesterol, triglycerides, testosterone and dehydroepiandrosterone sulphate (S-DHEA) plasma levels were measured in patients and in 6 non ovulating control women of similar age and weight. Only basal HDL levels were lower in patients than in controls (40.2 +/- 1.6 vs 51.4 +/- 3.3 mg/dl, p < 0.01). A decrease in S-DHEA levels was observed after flutamide in patients with hirsutism (3.2 +/- 0.4 to 2.1 +/- 0.4, p < 0.01) which may be attributed to the lowering of cortisol clearance induced by the drug. Total testosterone and plasma lipoproteins remained stable. Thus, peripheral androgenic blockade does not modify the decreased levels of HDL cholesterol in non ovulating patients with hirsutism.

Adult↗