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Biomedical subjects

A Garg

Publications and source records attributed to A Garg.

At least 19 recordsLinked to original sources
PubMed2001

Psychological stress perturbs epidermal permeability barrier homeostasis: implications for the pathogenesis of stress-associated skin disorders.

BACKGROUND: A large number of skin diseases, including atopic dermatitis and psoriasis, appear to be precipitated or exacerbated by psychological stress. Nevertheless, the specific pathogenic role of psychological stress remains unknown. In 3 different murine models of psychological stress, it was recently shown that psychological stress negatively impacts cutaneous permeability barrier function and that coadministration of tranquilizers blocks this stress-induced deterioration in barrier function. OBJECTIVES AND METHODS: The relationship between psychological stress and epidermal permeability barrier function was investigated in 27 medical, dental, and pharmacy students without coexistent skin disease. Their psychological state was assessed with 2 well-validated measures: the Perceived Stress Scale and the Profile of Mood States. Barrier function was assessed simultaneously with the stress measures at periods of presumed higher stress (during final examinations) and at 2 assumed, lower stress occasions (after return from winter vacation [approximately 4 weeks before final examinations] and during spring vacation [approximately 4 weeks after final examinations]). RESULTS: The subjects as a group demonstrated a decline in permeability barrier recovery kinetics after barrier disruption by cellophane tape stripping, in parallel with an increase in perceived psychological stress during the higher vs the initial lower stress occasions. During the follow-up, presumed lower stress period, the subjects again displayed lower perceived psychological stress scores and improved permeability barrier recovery kinetics, comparable to those during the initial lower stress period. Moreover, the greatest deterioration in barrier function occurred in those subjects who demonstrated the largest increases in perceived psychological stress. CONCLUSION: These studies provide the first link between psychological status and cutaneous function in humans and suggest a new pathophysiological paradigm, ie, stress-induced derangements in epidermal function as precipitators of inflammatory dermatoses.

Adult↗
PubMed2001

Adolescent occupational toxic exposures: a national study.

BACKGROUND: While many previous studies describe workplace-associated injuries in adolescents, few focus on toxic exposures. Such incidents are unlikely to be reported to either federal or state agencies. However, poison control centers often get called about these poisonings and might serve as a resource for monitoring their occurrence. OBJECTIVE: To describe the frequency and severity of job-related toxic exposures involving adolescents, the specific toxic agents involved, and trends over time. METHODS: Occupational toxic exposures occurring in the United States between 1993 and 1997 were analyzed using the Toxic Exposure Surveillance System database compiled by the American Association of Poison Control Centers. Contingency tables with the chi(2) statistic were used to test bivariate associations. Logistic regression was performed to investigate trends over time. RESULTS: Of 301 228 workplace toxic exposures reported over 5 years, 8779 (3%) involved adolescents younger than 18 years. The most common agents involved were alkaline corrosives (13.2%), gases and fumes (12.0%), cleaning agents (9.7%), bleaches (8.3%), drugs (7.4%), acids (7.2%), and hydrocarbons (6.9%). The injuries were rated as severe in 14.2% of exposures, life-threatening in 0.3%, and there were 2 deaths. The proportionate frequency of occupational exposures occurring among adolescents vs adults increased over time (odds ratio, 1.003; P<.001). CONCLUSIONS: Adolescent occupational toxic exposures are an underrecognized hazard in the United States. Poison control center experience can be used to fill a gap in the surveillance of such injuries.

Adolescent↗
PubMed2001

Testosterone perturbs epidermal permeability barrier homeostasis.

Although there are no known gender-related differences in permeability barrier function in adults, estrogens accelerate whereas testosterone retards barrier development in fetal skin, and male fetuses demonstrate slower barrier development than female littermates. Moreover, prenatal administration of the androgen receptor antagonist, flutamide, equalizes developmental rates in male and female fetuses. Therefore, we evaluated the effects of changes in testosterone on barrier homeostasis in adult murine and human skin. Hypogonadal mice (whether by castration or by treatment with systemic flutamide) displayed significantly faster barrier recovery at 3, 6, and 12 h than did controls, and testosterone replacement slowed barrier recovery in castrated mice. Moreover, testosterone directly effects the skin, as topical flutamide also accelerated barrier recovery in normal male mice. These findings appear to be of physiologic significance, since prepubertal male mice (age 5 wk) displayed accelerated barrier recovery in comparison with adult postpubertal (11 wk) males. These studies also appear to be relevant for humans, as a hypopituitary human subject demonstrated repeated changes in barrier recovery in parallel with peaks and nadirs in serum testosterone levels during intermittent testosterone replacement. Mechanistic studies showed that differences in epidermal lipid synthesis do not account for the testosterone-induced functional alterations. Instead, epidermal lamellar body (LB) formation and secretion both decrease, resulting in decreased extracellular lamellar bilayers in testosterone-replete animals. These studies demonstrate that fluctuations in testosterone modulate barrier function, and that testosterone repletion can have negative consequences for permeability barrier homeostasis.

Animals↗
PubMed2001

The challenges of emerging illness in urban environments: an overview.

The New York City West Nile outbreak is an important case study for examining several medical and public health issues raised by the specter of emerging illnesses in urban areas. Five specific issues are addressed in this issue of the Journal of Urban Health: ecosystem health, vector (e.g., mosquito) control, risk communication, public health infrastructure, and parallels between this outbreak and bioterrorism.

Animals↗
PubMed2001

Phenotypic heterogeneity in patients with familial partial lipodystrophy (dunnigan variety) related to the site of missense mutations in lamin a/c gene.

The lamin A/C (LMNA) gene has recently been reported to be mutated in familial partial lipodystrophy, Dunnigan variety (FPLD). We found mutations within exon 8 of LMNA (R482Q, R482W, and G465D) in 12 families with typical FPLD and in exon 11 (R582H) in 1 atypical family. To investigate phenotypic heterogeneity, we compared body fat distribution, using anthropometry and whole body magnetic resonance imaging, and metabolic parameters in women with atypical and typical FPLD. Compared with women with typical FPLD, the two sisters with atypical FPLD had less severe loss of sc fat from all the extremities and trunk and particularly from the gluteal region and medial parts of proximal thighs. Both types had similar excess of fat deposition in the neck, face, intraabdominal, and intermuscular regions. Women with atypical FPLD tended to have lower serum triglyceride and higher high density lipoprotein cholesterol concentrations. As exon 11 of LMNA does not comprise part of the lamin C-coding region, the R582H mutation affects only lamin A protein. Therefore, a unique phenotype of atypical FPLD may result from disrupted interaction of lamin A with other proteins and chromatin compared with typical FPLD, in which interaction of both lamins A and C may be disrupted.

Adipose Tissue↗
PubMed2000

Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus.

BACKGROUND: The effect of increasing the intake of dietary fiber on glycemic control in patients with type 2 diabetes mellitus is controversial. METHODS: In a randomized, crossover study, we assigned 13 patients with type 2 diabetes mellitus to follow two diets, each for six weeks: a diet containing moderate amounts of fiber (total, 24 g; 8 g of soluble fiber and 16 g of insoluble fiber), as recommended by the American Diabetes Association (ADA), and a high-fiber diet (total, 50 g; 25 g of soluble fiber and 25 g of insoluble fiber), containing foods not fortified with fiber (unfortified foods). Both diets, prepared in a research kitchen, had the same macronutrient and energy content. We compared the effects of the two diets on glycemic control and plasma lipid concentrations. RESULTS: Compliance with the diets was excellent. During the sixth week, the high-fiber diet, as compared with the the sixth week of the ADA diet, mean daily preprandial plasma glucose concentrations were 13 mg per deciliter [0.7 mmol per liter] lower (95 percent confidence interval, 1 to 24 mg per deciliter [0.1 to 1.3 mmol per liter]; P=0.04) and mean median difference, daily urinary glucose excretion 1.3 g (0.23; 95 percent confidence interval, 0.03 to 1.83 g; P= 0.008). The high-fiber diet also lowered the area under the curve for 24-hour plasma glucose and insulin concentrations, which were measured every two hours, by 10 percent (P=0.02) and 12 percent (P=0.05), respectively. The high-fiber diet reduced plasma total cholesterol concentrations by 6.7 percent (P=0.02), triglyceride concentrations by 10.2 percent (P=0.02), and very-low-density lipoprotein cholesterol concentrations by 12.5 percent (P=0.01). CONCLUSIONS: A high intake of dietary fiber, particularly of the soluble type, above the level recommended by the ADA, improves glycemic control, decreases hyperinsulinemia, and lowers plasma lipid concentrations in patients with type 2 diabetes.

Aged↗
PubMed2000

Lipodystrophies.

The lipodystrophies are rare disorders characterized by selective but variable loss of adipose tissue. Metabolic complications, such as insulin resistance, diabetes mellitus, hypertriglyceridemia, and fatty liver, increase in severity with the extent of fat loss. The lipodystrophies can be classified into two major types: familial and acquired. The main subtypes of familial lipodystrophies are congenital generalized lipodystrophy, an autosomal recessive disorder characterized by near complete lack of metabolically active adipose tissue from birth, and familial partial lipodystrophy, Dunnigan type, an autosomal dominant disorder characterized by loss of subcutaneous fat from the extremities at puberty and excess fat accumulation in the face and neck. Recently, a gene for congenital generalized lipodystrophy was localized to chromosome 9q34, and a gene for familial partial lipodystrophy, Dunnigan type, to chromosome 1q21-22; the genes, however, remain to be identified. Patients with acquired generalized lipodystrophy have generalized loss of subcutaneous fat, but those with acquired partial lipodystrophy have fat loss limited to the face, trunk, and upper extremities. Both varieties occur approximately three times more often in women, begin during childhood, and have underlying autoimmunity. Patients infected with the human immunodeficiency virus (HIV) who are receiving therapy that includes HIV-1 protease inhibitors have been reported to develop a lipodystrophy characterized by loss of subcutaneous fat from the extremities and face but excess fat deposition in the neck and trunk. Localized lipodystrophies can be caused by drugs, pressure, panniculitis, or unknown mechanisms. Current management of patients includes cosmetic surgery, diet, and drug therapy for control of diabetes and dyslipidemia.

Adipose Tissue↗
PubMed2000

Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.

Familial partial lipodystrophy (FPLD), Dunnigan variety, is an autosomal dominant disorder characterized by marked loss of subcutaneous adipose tissue from the extremities and trunk but by excess fat deposition in the head and neck. The disease is frequently associated with profound insulin resistance, dyslipidemia, and diabetes. We have localized a gene for FPLD to chromosome 1q21-q23, and it has recently been proposed that nuclear lamin A/C is altered in FPLD, on the basis of a novel missense mutation (R482Q) in five Canadian probands. This gene had previously been shown to be altered in autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD) and in dilated cardiomyopathy and conduction-system disease. We examined 15 families with FPLD for mutations in lamin A/C. Five families harbored the R482Q alteration that segregated with the disease phenotype. Seven families harbored an R482W alteration, and one family harbored a G465D alteration. All these mutations lie within exon 8 of the lamin A/C gene-an exon that has also been shown to harbor different missense mutations that are responsible for EDMD-AD. Mutations could not be detected in lamin A/C in one FPLD family in which there was linkage to chromosome 1q21-q23. One family with atypical FPLD harbored an R582H alteration in exon 11 of lamin A. This exon does not comprise part of the lamin C coding region. All mutations in FPLD affect the globular C-terminal domain of the lamin A/C protein. In contrast, mutations responsible for dilated cardiomyopathy and conduction-system disease are observed in the rod domain of the protein. The FPLD mutations R482Q and R482W occurred on different haplotypes, indicating that they are likely to have arisen more than once.

Alleles↗
PubMed2000

Fractures in large-segment allografts.

Segment skeletal defects that result from resection of a malignant bone neoplasm commonly are reconstructed with large segment allografts. Excellent functional results after these reconstructions and significant complications have been reported. Although it is known that a common complication seen with the use of allografts is allograft fracture, the factors associated with allograft fracture are not entirely clear. In this study, the hypothesis was examined that allograft reconstructions, which use internal fixation devices that penetrate the cortex of the allograft, are associated with an increased risk of fracture. Findings from large segment allograft reconstructions in 74 patients with a minimum followup of 36 months were studied. These 74 patients include 35 patients whose outcomes were reported previously and now have additional followup and 39 patients whose outcomes are being reported for the first time. Thirty-one of the 74 (42%) allografts fractured, and the mean time to fracture was 26 months. When the fixation techniques resulted in cortical penetration of the allograft, fractures occurred in 27 of the 43 (63%) allografts, and when fixation of the graft to the host bone required no cortical penetration, only four of the 31 (13%) allografts fractured. Fractures occurred in 12 of 15 (80%) tibial allografts and in only two of 17 (12%) proximal femoral allografts; however, the anatomic site was not statistically independent of method of fixation because 14 of the 15 tibial grafts had cortical penetration and 15 of the 17 proximal femoral grafts had no cortical penetration. The authors' analysis indicates that internal fixation devices that require cortical penetration are associated with an increased risk of allograft fracture.

Adolescent↗
PubMed2000

Gender differences in the prevalence of metabolic complications in familial partial lipodystrophy (Dunnigan variety).

Familial partial lipodystrophy, Dunnigan type (FPLD; Mendelian Inheritance in Man #151660), is an autosomal dominant disorder characterized by loss of s.c. fat from the extremities and trunk since puberty and predisposition to insulin resistance and its complications. However, for lack of recognition of affected men, previous studies could not ascertain any gender differences in phenotypic expression. Therefore, anthropometric variables and prevalence of diabetes mellitus, dyslipidemia, hypertension, and atherosclerotic vascular disease were compared among 17 postpubertal men and 22 women with FPLD from eight pedigrees. All individuals completed a questionnaire, and fasting blood was analyzed for glucose, insulin, and lipoprotein concentrations. Both affected men and women had similar patterns of fat loss. Compared with the affected men, women had higher prevalence of diabetes (18% and 50%, respectively; P = 0.05) and atherosclerotic vascular disease (12% and 45%, respectively; P = 0.04) and had higher serum triglycerides (median values, 2.27 and 4.25 mmol/L, respectively; P = 0.02) and lower high-density lipoprotein cholesterol concentrations (age-adjusted means, 0.94 and 0.70 mmol/L, respectively; P = 0.04). The prevalence of hypertension and fasting serum insulin concentrations were similar. In conclusion, women with FPLD are more severely affected with metabolic complications of insulin resistance than men. These observations raise the possibility that women with generalized and regional obesity may also have more severe metabolic sequelae of insulin resistance.

Adult↗
PubMed2000

Skeletal muscle morphology and exercise response in congenital generalized lipodystrophy.

OBJECTIVE: Congenital generalized lipodystrophy (CGL) is an autosomal recessive genetic disorder characterized by almost complete absence of adipose tissue, muscular appearance, and severe insulin resistance since birth. We investigated whether insulin resistance in CGL patients is associated with abnormal muscle morphology and whether increased muscularity imparts increased muscle strength and exercise capacity RESEARCH DESIGN AND METHODS: We obtained quadriceps muscle biopsies to study muscle fiber types and capillary density in three African-American women (aged 17-20 years) with CGL. We also assessed quadriceps muscle strength, muscle metabolism, and maximal O2 consumption in the patients. RESULTS: Quadriceps muscle biopsies revealed a markedly higher percentage of type II (fast-twitch glycolytic) muscle fibers in patients with CGL versus sedentary young women (75-78 vs. 47-57%, respectively). The capillary-to-fiber ratio (2.7-3.0), however, was normal. Cross-sectional areas of type I (slow-twitch oxidative) (1,262-2,685 microm2) and type II (2,304-3,594 microm2) fibers were far below the normal values (3,811-4,310 and 3,115-4,193 microm2, respectively), suggesting muscle hyperplasia but not hypertrophy The quadriceps muscle strength, as measured by Cybex, was below average; the maximal O2 consumption (23-32 ml x kg(-1) x min(-1)) was also below average. 31P nuclear magnetic resonance spectroscopy of the forearm muscles revealed normal pH and metabolic responses to static and dynamic exercises. CONCLUSIONS: We conclude that insulin resistance in patients with CGL is associated with an increased proportion of type II muscle fibers but not reduced capillary density. Increased muscularity in CGL is due to muscle hyperplasia and is not associated with increased muscle strength.

Adipose Tissue↗
PubMed2000

Synovial sarcoma. Large size predicts poor outcome.

A consecutive series of 38 patients with synovial sarcoma diagnosed and treated in a consistent fashion from 1976 to 1994 was reviewed for prognostic variables. The histologic specimens were reviewed and confirmed by one pathologist. There was a minimum 4-year followup for all surviving patients and no patients were lost to followup. The treatment protocol consisted of surgical excision with a wide or radical margin and limb preservation when possible. In those patients in whom the surgical margin was undefined or was less than a wide margin, perioperative radiation therapy was used. Four patients presented with metastatic disease and all died of their disease. Thirty-four patients had localized disease at presentation. Variables considered in stratifying outcomes included histologic grade, histologic subtype, surgical margin, presence or absence of local recurrence, age, and size of tumor. Of the 34 patients without metastasis there was a strong statistical association between size of tumor and survival: 17 patients with tumors less than 5 cm indiameter had a 100% survival, 12 patients with tumors 5 cm to 10 cm had a 75% survival, and five patients with tumors greater than 10 cm had a 20% survival. The authors urge that a multicenter trial for neoadjuvant chemotherapy be initiated for patients presenting with a synovial sarcoma greater than 10 cm in diameter.

Adolescent↗
PubMed1999

Right atrial compartmentalization using radiofrequency catheter ablation for management of patients with refractory atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is often refractory to antiarrhythmic drugs, and patients who are intolerant of AF may require the maze operation for cure. As a less invasive alternative, a catheter-based, right atrial compartmentalization procedure was evaluated. METHODS AND RESULTS: Twelve patients with AF refractory to Class I and III antiarrhythmic drugs were studied. Four linear right atrial radiofrequency ablations were performed, from superior to inferior vena cava in the posterior wall and interatrial septum, anteriorly from the superior vena cava to the tricuspid annulus through the appendage, and across the tricuspid valve-inferior vena cava isthmus. The radiofrequency catheter was dragged along each line three to four times, until the atrial electrogram amplitude decreased by 75% and there was bidirectional conduction block in the tricuspid valve-inferior vena cava isthmus. One complication occurred: sinus node dysfunction requiring a pacemaker. Eight patients were discharged from the hospital on no antiarrhythmic drugs, and four were discharged on previously ineffective antiarrhythmic drugs. Total duration of follow-up was 21.3 +/- 11.2 months. Four patients discharged on previously ineffective antiarrhythmic drugs had no recurrence of AF. One patient discharged off antiarrhythmic drugs had no recurrence of AF. Seven patients discharged off antiarrhythmic drugs had recurrent AF by 12.6 +/- 13.0 months (median 6, range 1 to 39); 3 of these 7 responded to previously ineffective antiarrhythmic drugs without further AF and 4 did not. Thus, 8 of 12 patients (67%) had suppression of AF after ablation on previously ineffective medication or no medication. CONCLUSION: Right atrial compartmentalization may alter the substrate for AF, thus improving the efficacy of previously ineffective antiarrhythmic drugs. Because it is relatively safe, it may be a reasonable adjunctive intervention to maintain sinus rhythm in patients with drug-refractory AF.

Adult↗
PubMed1999

Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo.

We validate the use of 1H magnetic resonance spectroscopy (MRS) to quantitatively differentiate between adipocyte and intracellular triglyceride (TG) stores by monitoring the TG methylene proton signals at 1.6 and 1.4 ppm, respectively. In two animal models of intracellular TG accumulation, intrahepatic and intramyocellular TG accumulation was confirmed histologically. Consistent with the histological changes, the methylene signal intensity at 1.4 ppm increased in both liver and muscle, whereas the signal at 1.6 ppm was unchanged. In response to induced fat accumulation, the TG concentration in liver derived from 1H MRS increased from 0 to 44.9 +/- 13.2 micromol/g, and this was matched by increases measured biochemically (2.1 +/- 1.1 to 46.1 +/- 10.9 micromol/g). Supportive evidence that the methylene signal at 1.6 ppm in muscle is derived from investing interfascial adipose tissue was the finding that, in four subjects with generalized lipodystrophy, a disease characterized by absence of interfacial fat, no signal was detected at 1.6 ppm; however, a strong signal was seen at 1.4 ppm. An identical methylene chemical shift at 1.4 ppm was obtained in human subjects with fatty liver where the fat is located exclusively within hepatocytes. In experimental animals, there was a close correlation between hepatic TG content measured in vivo by 1H MRS and chemically by liver biopsy [R = 0.934; P <.0001; slope 0.98, confidence interval (CI) 0.70-1.17; y-intercept 0.26, CI -0.28 to 0. 70]. When applied to human calf muscle, the coefficient of variation of the technique in measuring intramyocellular TG content was 11.8% in nonobese subjects and 7.9% in obese subjects and of extramyocellular (adipocyte) fat was 22.6 and 52.5%, respectively. This study demonstrates for the first time that noninvasive in vivo 1H MRS measurement of intracellular TG, including that within myocytes, is feasible at 1.5-T field strengths and is comparable in accuracy to biochemical measurement. In addition, in mixed tissue such as muscle, the method is clearly advantageous in differentiating between TG from contaminating adipose tissue compared with intramyocellular lipids.

Adipose Tissue↗