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Biomedical subjects

J Wortsman

Publications and source records attributed to J Wortsman.

At least 127 records · Page 7Linked to original sources
PubMed1985

Altered skin elastic fibers in hypothyroid myxedema and pretibial myxedema.

Elastic fibers account for 2% of dermal volume and are responsible for normal skin resiliency. We investigated a disorder of the dermal elastic component as the mechanism for the decreased elasticity of skin in myxedema. Skin biopsy specimens were obtained from patients with thyroid diseases and normal subjects matched for age, sex, and biopsy location. Elastic fiber concentration, determined by computerized morphometric analysis of Verhoeff-van Gieson-stained sections, was significantly lower than normal in hypothyroid and pretibial myxedema. The decreased elastin concentration was not a consequence of the glycosaminoglycan infiltration. Ultrastructural studies of myxedematous skin showed wide variability of elastic fiber diameter and decreased microfibrils. Myxedema (hypothyroid and pretibial) is consistently associated with quantitative and qualitative defects of dermal elastic fibers.

Adult↗
PubMed1985

Elevation of a calcium fraction tightly bound to serum proteins in maternal blood at delivery and in cord blood from newborn infants.

The intimate mechanisms for calcium transport and accumulation in bone cells are complex. We have previously observed that calcium tightly bound to serum proteins is taken up by bone cells preferentially over ionized calcium. To explore the significance of this phenomenon as a potential mechanism for calcium transport in vivo, we studied the distribution of calcium in sera from normal individuals, pregnant women, cord blood from newborn infants, and patients with disorders of calcium homeostasis. Tightly bound calcium was defined as the fraction that remained bound to serum proteins after six consecutive ultrafiltration cycles. Cord blood from newborn infants showed striking elevations of total serum calcium, 11.2 +/- 0.3 mg/dl (+/- SEM), and of the fraction tightly bound to serum proteins, 25.1% +/- 1.7%, compared to normal control values of 9.5 +/- 0.1 mg/dl, and 18.9% +/- 1.1%, respectively (p less than 0.01). Maternal blood at delivery also exhibited an increase of the tightly bound calcium fraction, 27.1% +/- 0.7% (p less than 0.01), but normal total serum calcium concentration, 9.4 +/- 0.2 mg/dl. There was no correlation between the simultaneous fractional concentrations of tightly bound calcium in the maternal and fetal blood compartments (r = -0.03; p = 0.92; n = 12 sets of paired samples). The high concentrations of calcium tightly bound to serum proteins in cord blood suggests that this fraction could play a role in the mineralization of fetal bone.

Biological Transport↗
PubMed1984

Adrenomedullary response to maximal stress in humans.

The most important neuroendocrine response to stress is an increase in plasma epinephrine concentration. To investigate the clinical significance of this response, plasma catecholamine levels were measured (single-isotope derivative assay) in chronic stress (severe illness; n = 22) and acute maximal stress (cardiac arrest; n = 23). The results were then compared with the values from 60 normal resting subjects: epinephrine (mean +/- SEM) 0.034 +/- 0.002 ng/ml; norepinephrine 0.228 +/- 0.01 ng/ml. Chronic stress (intensive care unit patients) was associated with a fourfold elevation of epinephrine concentration (0.14 +/- 0.06 ng/ml; range 0.01 to 1.37; p less than 0.01 versus normal control subjects). Acute maximal stress (resuscitation following cardiac arrest) resulted in a greater than 300-fold increase in the plasma epinephrine level (10.3 +/- 2.9 ng/ml; range 0.36 to 35.9; n = 15; p less than 0.01). Peak plasma epinephrine levels in successfully resuscitated patients (n = 6) ranged from 0.36 to 273 ng/ml (three patients had received epinephrine therapy). The plasma norepinephrine level was increased twofold in intensive care unit patients (0.52 +/- 0.06 ng/ml; p less than 0.01) and 32-fold after cardiac arrest (7.37 +/- 1.8 ng/ml; p less than 0.01). During resuscitation, the correlation between the simultaneous epinephrine and norepinephrine levels was highly significant: r = 0.76; p less than 0.01. It is concluded that (1) chronic, severe stress produces only moderate elevations of plasma epinephrine levels (up to 1.37 ng/ml), whereas acute stress produces marked increases of plasma epinephrine that may reach the extraordinarily high level of 35.9 ng/ml, (2) the potential toxicity from the adrenomedullary response to acute stress is further exacerbated by the parallel release of norepinephrine, and (3) under close medical monitoring, it is possible to survive with plasma epinephrine concentrations as high as 273 ng/ml.

Adrenal Medulla↗
PubMed1984

Histochemical evaluation of glycosaminoglycan deposition in the skin.

Histologic demonstration of glycosaminoglycan (GAG) deposition in the skin has been based on the use of either colloidal iron or alcian blue. To define the best technique for the determination of skin GAG content we undertook a prospective study comparing the two stains and evaluating the use of cetylpyridinium chloride (CPC) to enhance fixation. Slides were prepared from skin biopsies obtained from five patients with cutaneous mucinoses. The preparations were coded and examined by three observers. Colloidal iron staining gave a higher intensity for GAG deposits in papillary and reticular dermis. Digestion by specific enzymes identified similar GAGs with either colloidal iron, or alcian blue; however, colloidal iron made GAGs more obvious, partly due to the contrast afforded by the yellow background stain. The addition of CPC to the fixative appreciably enhanced GAG fixation without interfering with the action of enzymes. Experimentally, we confirmed this effect of CPC by determining a pronounced decrease in GAG leakage into the fixative from CPC treated human umbilical cord. We conclude that the combination of CPC fixation and colloidal iron staining gives the best definition of skin GAGs in clinical specimens.

Acromegaly↗
PubMed1984

Decreased nuclear uptake of [125I]triiodo-L-thyronine in fibroblasts from patients with peripheral thyroid hormone resistance.

The cellular mechanisms that cause the syndrome of generalized, peripheral, and pituitary resistance to thyroid hormones are unclear. In order to investigate the possibility of a defect at the nuclear receptor for T3, we examined: 1) equilibrium binding of [125I]T3 (64 analyses) to the nuclei of intact cultured fibroblasts from 12 patients with both sporadic and familial generalized or selective pituitary resistance, 17 normal subjects, and two apparently normal siblings from affected families; and 2) kinetics of [125I]T3 nuclear uptake (22 analyses) in intact fibroblasts from 4 generalized resistant patients from two different kindreds, compared to one apparently normal sister of one affected patient and 6 normal subjects. Statistical analysis of the equilibrium binding parameters showed no differences in nuclear binding capacity for T3 among all groups. The equilibrium dissociation constants (Kd) also were not significantly different in fibroblasts from the selective pituitary resistant patients, the normal siblings, and the normal subjects. In contrast, the KdS from the general resistant patients were significantly increased (median = 1.94 X 10(-10) M, 5-95% confidence interval = 1.18-2.93 X 10(-10) M 1.11, 0.77-1.25 X 10(-10) M; P less than 0.008). Since there was considerable overlap of the equilibrium binding values among groups, we studied the kinetics of [125I]T3 nuclear uptake in selected cell lines from normal subjects and familial generalized resistant patients. Kinetic analysis of the association curve revealed that, compared to the normal subjects, maximum binding at 10(-10) M [125I]T3 was significantly reduced to 50% in two resistant patients, to 10% in another two patients, and to 65% in one apparently-normal sibling. The empiric parameter lambda that corresponds to the slope at the origin of the curve was not significantly different in any patient compared to normal. The calculated apparent association constant, derived from lambda, and the binding capacity obtained at equilibrium, showed differences that were significant for only one of the patients. We conclude that cultured fibroblasts from patients with familial generalized resistance to thyroid hormone display abnormal kinetics of T3 nuclear uptake which provide a convenient in vitro method for the recognition of thyroid hormone resistance at the cell level. Furthermore, because cultured fibroblasts can be grown under controlled experimental conditions, they are a suitable tissue for further study of the molecular basis of these disorders.

Adolescent↗
PubMed1984

Acute arthritis during isotretinoin treatment for acne.

Treatment with isotretinoin (retinoic acid), which is frequently used in the control of acne, is associated with transient arthralgias in up to 16% of patients. We encountered two cases of acute, aseptic arthritis of the knee in male patients receiving isotretinoin, during the third week and third month of therapy. Synovial fluid obtained from one of the patients was noninflammatory. The drug concentration in the synovial fluid was 131 ng/mL--a level that was compatible with diffusion from the blood (simultaneous serum concentration, 229 ng/mL). Arthritis resolved in both patients without sequelae, despite continuation of drug treatment in one of them. This observation indicates that arthritis with joint effusion may complicate isotretinoin use; it also suggests that alternative measures should be considered before administering the drug to patients with rheumatologic disorders.

Acne Vulgaris↗
PubMed1984

Elevated levels of plasma beta-endorphin and gamma 3-melanocyte stimulating hormone in the polycystic ovary syndrome.

The authors have suggested that dysfunction of a central structure (above the pituitary level) is the primary etiologic factor responsible for the production of the polycystic ovary syndrome. To investigate further the functional integrity of the hypothalamic pituitary axis, plasma levels of beta-endorphin, gamma 3-melanocyte stimulating hormone, and gamma 1-melanocyte stimulating hormone-like immunoreactivity were measured in six patients with polycystic ovary syndrome, and in ten women with normal ovarian function. The limit of sensitivity for the radioimmunoassays was 20 pg/mL. Plasma beta-endorphin was significantly higher in polycystic ovary syndrome than in control subjects: (mean +/- SE) 60 +/- 10 versus 30 +/- 4 pg/mL, respectively (P less than .05). gamma 3-Melanocyte stimulating hormone was detectable in four of six patients with polycystic ovary syndrome (mean for the whole group: 45 +/- 15 pg/mL); it was undetectable in all the control subjects. Control of plasma beta-endorphin and gamma 3-melanocyte stimulating hormone secretion in PCO was evaluated with metyrapone and dexamethasone. Overnight administration of metyrapone to polycystic ovary syndrome patients resulted in rises of beta-endorphin and gamma 3-melanocyte stimulating hormone. Dexamethasone suppressed only partially (to basal concentrations) beta-endorphin and gamma 3-melanocyte stimulating hormone levels. Plasma adrenocorticotropic hormone concentrations were within the normal range and displayed the expected changes in response to metyrapone and dexamethasone. The present report presents an additional central (hypothalamic-pituitary) abnormality in patients with the polycystic ovary syndrome.

Adrenocorticotropic Hormone↗
PubMed1984

The acquired cutaneous mucinoses.

Glycosaminoglycan (GAG) infiltration of the skin is a feature of hyperthyroidism, hypothyroidism, pretibial myxedema, scleromyxedema, and scleredema. We investigated the pathogenesis of the GAG deposits using light microscopy, histochemical digestion with a series of GAG-specific enzymes, and electron microscopy. Hyaluronic acid was the main GAG in all the conditions and in normal skin. Furthermore, there was minimal histologic variability of GAG dermal distribution. A striking distinguishing feature involved dermal fibroblast activity, which appeared normal or inactive in thyroid disorders and hypertrophic and/or hyperplastic in scleromyxedema and scleredema. Thus, the acquired cutaneous mucinoses exhibit similar skin GAG distribution and biochemical composition. The morphologic differences in fibroblastic activity suggest that the mucinoses of scleredema and scleromyxedema represent a local process, whereas the GAG infiltration of thyroid diseases may have a systemic origin.

Adult↗
PubMed1983

Familial resistance to thyroid hormone associated with decreased transport across the plasma membrane.

Resistance to thyroid hormone associated with a defect in hormone transport across the plasma membrane occurred in a 74-year-old eumetabolic woman. She had marked elevations in the serum levels of total thyroxine (T4), free T4, and reverse triiodothyronine (rT3). Levels of T3 were only minimally increased. The hyperthyroxinemia was thyrotrophin (TSH) dependent, but was not due to an alteration in the binding of T4 to serum proteins. Refractoriness to thyroxine was only partial, as indicated by the increase in the basal metabolic rate and suppression of the response of TSH to thyrotrophin-releasing hormone (TRH) after the administration of L-thyroxine, 600 micrograms daily, for 3 weeks. The basic abnormality involved a selective decrease of T4 plasma membrane transport shown by in-vitro studies of erythrocytes. Screening of family members showed similar biochemical abnormalities in two other relatives. In this familial syndrome characterized by eumetabolic hyperthyroxinemia, the alteration of thyroid hormone metabolism seems to involve primarily the partition of T4 between the intra- and extracellular spaces.

Adult↗
PubMed1983

Acanthosis nigricans in a patient with streak gonads.

Acanthosis nigricans (ACN) is associated with ovarian disorders or abnormalities of carbohydrate metabolism. We saw a 21-year-old woman who had primary amenorrhea and ACN. Results of endocrine studies showed anovulation and low serum estradiol levels with increased gonadotropin concentrations. Laparoscopic examination disclosed bilateral streak gonads; the ovaries were completely replaced by fibrous tissue. Cultures of peripheral lymphocytes, skin fibroblasts, and the right and left ovaries demonstrated normal female karyotype 46XX in all mitoses studied. An autoimmune disorder was excluded by the absence of antithyroid and antiadrenal antibodies. Specific antibodies against ovarian proteins were also absent. A glucose tolerance test demonstrated fasting hyperinsulinemia and exaggerated serum insulin response to the glucose load. The observations in this patient exclude a primary pathogenic role for the ovary in the production of ACN; they also lend further support to a connection between the cutaneous disorder and insulin resistance.

Acanthosis Nigricans↗
PubMed1983

Glycosaminoglycan deposition in the acanthosis nigricans lesions of the polycystic ovary syndrome.

Skin biopsy specimens of acanthosis nigricans (AN) lesions were obtained from seven women with the polycystic ovary (PCO) syndrome and insulin resistance (IR). All the patients had normal thyroid function test results and fasting hyperinsulinemia with an exaggerated insulin response to oral glucose. Acanthosis nigricans lesions exhibited prominent deposits of glycosaminoglycan (GAG) consisting mostly of hyaluronic acid in the papillary dermis. Normal amounts of GAGs were found in control biopsy specimens obtained from areas of the skin not involved by AN and from skin of the nape of the neck or axillae in three normal women. These studies demonstrate that GAG deposition is a regular component of AN skin in patients with PCO and IR. The cause of these infiltrates remains to be determined.

Acanthosis Nigricans↗
PubMed1982

Cancer in cystic lesions of the thyroid.

We reviewed the records of 341 patients who underwent thyroidectomy for the suspicion of cancer between 1975 and 1980. Cancer of the thyroid was found in 14% of them. Although cysts of the thyroid (pathologic finding of a fluid-filled cavity greater than 1 cm in diameter) were encountered in 35% of the patients, cysts were similarly distributed among patients with benign conditions (27%) or with cancer (33%). Most of the thyroid cysts in patients with carcinoma measured 2 to 4 cm in diameter. The cancer was found within the cystic cavity. The cysts in patients with cancer appeared to originate from necrosis of the tumor. B-mode ultrasonography was not reliable in differentiating cystic and solid lesions. The demonstration of the cystic nature of a thyroid nodule does not rule out the diagnosis of cancer of the gland.

Adenoma↗
PubMed1982

Incomplete differentiation of Wolffian structures: a form of Kallmann's syndrome?

We have reported a sibship in which all three males had azoospermia and a normal 46,XY karyotype. The mechanisms for the production of azoospermia were Kallmann's syndrome and bilateral agenesis of the globus major (head of the epididymis) in the proband and bilateral agenesis of the vasa deferentia and seminal vesicles in the two brothers. It is suggested that this syndrome of agenesis of the testicular excretory system may be a variant of Kallmann's syndrome.

Adult↗
PubMed1982

Abnormalities of fuel metabolism in the polycystic ovary syndrome.

To investigate the metabolic effects of medroxyprogesterone acetate, carbohydrate and lipid metabolism in women with polycystic ovary syndrome was evaluated before and after long-term therapy with this drug. The effects of suppression of pituitary gonadotropins and ovarian sex steroids were correlated with the response to an oral glucose load and with a serum lipid profile. Twenty of 25 women with polycystic ovary syndrome weighted more than 150% of their ideal body weight. None of the patients had fasting hyperglycemia. Fasting and peak serum insulin responses to glucose were abnormally high in most patients with polycystic ovary syndrome. Fasting serum insulin had a significant positive correlation with percent ideal body weight (r = .7, P less than .01). High density lipoprotein cholesterol was low in all patients studied, whereas total cholesterol and serum triglyceride levels were normal. Therapy with medroxyprogesterone acetate did not affect body weight, glucose tolerance, or serum lipids. The correlations between serum testosterone and high-density lipoprotein cholesterol or insulin levels were not significant (P greater than .1). The authors conclude that medroxyprogesterone acetate does not affect the metabolic syndrome of obesity, hyperinsulinemia, and decreased high-density lipoprotein cholesterol that is commonly seen in patients with polycystic ovary syndrome.

Adult↗
PubMed1982

Histochemical characterization of the cutaneous involvement of acromegaly.

We evaluated the pathogenesis of skin thickening in three patients with acromegaly. Growth hormone levels were normal in one patient and were elevated in two patients. Skin biopsy specimens were obtained from the forearm. Hematoxylineosin staining showed slight epidermal thinning and, in two of the patients, a small increase in the number of fibroblasts. Selective stains for collagen, elastic, and reticular fibers disclosed normal connective tissue. The most striking abnormality was increased glycosaminoglycan deposition on the slides stained with colloidal iron. Glycosaminoglycan infiltration occurred mostly in the papillary and upper reticular dermis and was not directly related to the simultaneous growth hormone levels. Tissue digestion with specific enzymes identified hyaluronic acid, chondroitin-4- and 6-sulfate, and dermatan sulfate as the most prominent glycosaminoglycans in the dermis. The skin ultrastructure appeared to be preserved on electron microscopy. We conclude that cutaneous mucinoses is the main cause for the thickening of the skin in acromegaly.

Acromegaly↗
PubMed1982

Lipoatrophic diabetes: endocrine dysfunction and the response to control hypertriglyceridemia.

Endocrine function was studied in a 24 year old female with lipoatrophic diabetes (LD). Baseline endocrine studies (serum triglycerides: 2600 mg/dl) demonstrated hyperprolactinemia (serum prolactin 51 ng/ml), increased ACTH levels, absence of suppression of ACTH to a high dose of dexamethasone which suppressed serum cortisol normally and, hyperresponsiveness of TSH to stimulation with TRH. Thyroid hormone levels (total and free fraction) were essentially normal. Major metabolites of thyroid hormone (T3, rT3, 3, 3'-T2, and 3', 5'-T2) were also normal and exhibited a normal response to the administration of L-thyroxine and propylthiouracil. Exchange of 84% of the patient's plasma resulted in a decrease in serum triglycerides (700 mg/dl) which was followed by a rebound to the original level in seven days. After the sixth plasmapheresis serum triglycerides stabilized at less than 1000 mg/dl. Plasmapheresis was associated with the appearance of amenorrhea and galactorrhea; also hypertension and proliferative retinopathy developed during this therapy. Repeat endocrine function studies (serum triglycerides: 700 mg/dl) showed a further rise in serum prolactin (greater than 160 ng/ml), persistence of abnormal ACTH secretion and normalization of TSH responsiveness. Lipoatrophic diabetes is associated with abnormal central endocrine function but appropriate peripheral target gland secretion. A course of plasmapheresis improves the hypertriglyceridemia but not the endocrine dysfunction. In this patient with LD the most important side effect of plasmapheresis was the development of cardiovascular complications.

Adrenocorticotropic Hormone↗
PubMed1981

Hashimoto's thyroiditis simulating cancer of the thyroid.

We reviewed a group of 30 patients with Hashimoto's thyroiditis who underwent thyroidectomies for suspicion of cancer. A prominent nodule was present in all of the patients; compression symptoms were present in 13 and pain in the thyroid in six. The nodule was cold on scan in 21 patients. Lack of responsiveness to suppressive therapy or nodule enlargement occurred in 18 patients. In addition to the nodule, operative findings included adherence to surrounding tissues in seven patients, lymphadenopathy in seven, increased vascularity in four, and extension to distant cervical structures in two. Pathologic findings in the nodule were similar to those in the rest of the gland; they consisted of lymphocytic infiltration, fibrosis, and variable follicular size. Examination of lymph nodes demonstrated lymphoid hyperplasia. We emphasize the similarities between chronic thyroiditis and carcinoma of the thyroid; the occasional coexistence of these two conditions stresses the need for newer methods in the differential diagnosis.

Adult↗