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Biomedical subjects

A Garg

Publications and source records attributed to A Garg.

At least 19 recordsLinked to original sources

Syntheses and structural and electrochemical characterizations of vanadatricarbadecaboranyl analogues of vanadocene and the structural characterization of the [Li(CH(3)CN)2+](6-CH(3)-nido-5,6,9-C(3)B(7)H(9-) tricarbadecaboranyl anion.

A single-crystal X-ray determination of the [Li(CH(3)CN)(2)(+)](6-CH(3)-nido-5,6,9-C(3)B(7)H(9)(-)) salt has shown that the 6-CH(3)-nido-5,6,9-C(3)B(7)H(9)(-) tricarbadecaboranyl anion has a nido-cage geometry based on an octadecahedron missing the unique six-coordinate vertex. The resulting six-membered open face is puckered, with two of the cage carbons (C6 and C9) occupying the low-coordinate cage positions above the plane of the four remaining atoms (C5, B7, B8, and B10). The Li(+) ion is centered over the open face and is solvated by two acetonitrile molecules. The reactions of the 6-CH(3)-nido-5,6,9-C(3)B(7)H(9)(-) anion with various vanadium halide salts, including VCl(4), VCl(3), and VBr(2), each resulted in the isolation of the same five paramagnetic products (2-6) of composition V(CH(3)-C(3)B(7)H(9))(2). X-ray crystallographic determinations of 2-5 showed that the complexes consist of two octadecahedral VC(3)B(7) fragments sharing a common vanadium vertex and established their structures as commo-V-(1-V-4'-CH(3)-2',3',4'-C(3)B(7)H(9))(1-V-2-CH(3)-2,3,4-C(3)B(7)H(9)) (2), commo-V-(1-V-5'-CH(3)-2',3',5'-C(3)B(7)H(9))(1-V-4-CH(3)-2,3,4-C(3)B(7)H(9)) (3), commo-V-(1-V-5'-CH(3)-2',3',5'-C(3)B(7)H(9))(1-V-2-CH(3)-2,3,4-C(3)B(7)H(9)) (4), and commo-V-(1-V-2-CH(3)-2,3,4-C(3)B(7)H(9))(2) (5). These complexes can be considered as tricarbadecaboranyl analogues of vanadocene, (eta(5)-C(5)H(5))(2)V. However, unlike vanadocene, these complexes are air- and moisture-stable and have only one unpaired electron. The five complexes differ with respect to one another in that they either (1) contain different enantiomeric forms of the CH(3)-C(3)B(7)H(9) cages, (2) have a different twist orientation of the two cages, or (3) have the methyl group of the CH(3)-C(3)B(7)H(9) cage located in either the 2 or 4 position of the cage. Subsequent attempts to oxidize the compounds with reagents such as Br(2) and Ag(+) were unsuccessful, illustrating the ability of the tricarbadecaboranyl anion to stabilize metals in low oxidation states. Consistent with this, both the electrochemical oxidation and the reduction of 2 were much more positive than those of the same oxidation state changes in vanadocene. The one-electron reduction of 2 is a remarkable 2.9 V positive of that of Cp(2)V.

Journal Article↗

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↗

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↗

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↗

The epidemiology of proximal humeral fractures.

We present a 5-year prospective study of the epidemiology of 1,027 proximal humeral fractures. These fractures, which tend to occur in fit elderly persons, have a unipolar age distribution and the highest age-specific incidence occurs in women between 80 and 89 years of age. The commonest was the B1.1 impacted valgus fracture, found in one-fifth of the cases in this series, a type that is not included in the Neer classification. We used both Neer and AO classifications. The AO classification proved to be more comprehensive because in the Neer classification, half of the fractures are minimally displaced and almost nine-tenths fall into only three categories. In the AO classification, the B1.1, A2.2, A3.2 and A1.2 sub-groups comprise over half of all proximal humeral fractures, while the AO type C fractures occur in only 6%. We suggest that the literature does not adequately reflect the spectrum of proximal humeral fractures.

Activities of Daily Living↗

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↗

Anatomical variation of the sphenomandibular ligament.

The sphenomandibular ligament, which is derived from the sheath of Meckel's cartilage, is a fibrous structure that passes between the spine of the sphenoid bone and the lingula of the mandible. Although anatomical texts provide basic descriptions of this structure, there are few published reports of the extent of its variability or its possible clinical implications. The aim of this study was to provide a detailed description of the nature and extent of anatomical variability in the sphenomandibular ligament of seven human cadavers. Dissections of sagittally sectioned heads were performed using a medial approach that involved displacement of the tongue and mucosal tissues in the oral cavity and oropharynx, then reflection of the medial pterygoid muscle. The ligaments ranged in shape from thin bands that descended for a short distance from the spine of the sphenoid to broad bi-concave ligaments with prominent insertions. The mylohyoid nerve was seen to pass behind the ligament in all specimens, emerging from the postero-inferior border of the mandibular attachment before running into the mylohyoid groove on the medial surface of the ramus. Lying in the pterygomandibular space, the ligament was surrounded by fascia, both structures presenting potential barriers to the diffusion of local anaesthetic solution if injected medially. The appearance of the lingula also varied, and did not seem to reflect the size of attachment of the ligament, suggesting an alternative explanation of lingula morphology, perhaps related to a continuation of the mylohyoid ridge and anterior border of the mylohyoid groove.

Humans↗

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↗

The translated two-part fracture of the proximal humerus. Epidemiology and outcome in the older patient.

We have undertaken a five-year prospective study of 126 translated two-part fractures of the proximal humerus and present an analysis of the epidemiology and of the factors which affect outcome in elderly patients. The fracture has a unimodal age distribution and rarely affects adults under the age of 50 years. Analysis showed that patients with two-part translated fractures of the surgical neck tended to be independent and relatively fit, despite the fact that their mean age was 72 years. Outcome was determined by the age of each patient and the degree of translation on the initial anteroposterior radiograph. Surgery did not improve the outcome, regardless of the degree of translation.

Activities of Daily Living↗

Lacunar syndromes due to small haemorrhagic lesions.

OBJECTIVE: To study the frequency, clinical presentations and prognostic aspects of haemorrhagic lacunar syndromes. MATERIAL AND METHODS: 375 patients of cerebrovascular accidents admitted in neurology wards over 2 years were studied. Based on CT findings, 114 patients were diagnosed as intra cerebral haemorrhage (ICH). They were assessed in detail by careful history and examination of neurological status. Coagulation studies, MRI and angiography were done in selected cases. RESULTS: In 17 (15%) patients, size of hematoma was < 2 cms as seen in CT scan. The sites of these small haemorrhages were in basal ganglia (6 patients), internal capsule (3 patients), thalamus (5 patients) and pons (3 patients). Depending on their location they presented as pure motor stroke, pure sensory stroke, ataxic hemiparesis, sensorimotor stroke and clumsy hand-dysarthia syndrome. Three patients showed interesting phenomena like transient ischemic attack caused by bleed or previous disease showing improvement after bleed. Prognosis of these small ICH was excellent with 100% survival rate and lesser disability as shown by good functional recovery. CONCLUSIONS: Haemorrhagic lacunar syndromes are not just the statistical curiosities but could have significant prognostic bearing.

Female↗

Improving antibiotic and bronchodilator prescription in children presenting with difficult breathing: experience from an urban hospital in India.

OBJECTIVE: To evaluate the relative frequency of other conditions that share a clinical overlap with pneumonia as defined by the WHO case management algorithm and to determine the possibility of refining the antibiotic and bronchodilator prescription on the basis of simple clinical features. DESIGN: Prospective observational. SETTING: Urban tertiary care center. METHODS: Two hundred children, between the ages of 6 months to 5 years, presenting with difficult breathing (as defined by WHO algorithm) were prospectively evaluated for the diagnosis and the need for bronchodilator and antibiotic therapy (clinician s diagnosis). An additional independent blinded evaluation of the chest X-rays was done by a radiologist after the study (radiologist-aided diagnosis). On the basis of reliable predictors (sensitivity > 70% and specificity > 70%) of antibiotic and bronchodilator prescription, irrespective of the exact diagnostic category, two viable modifications of WHO case management algorithm emerged, which were compared by paired proportion test. RESULTS: Acute asthma was the predominant condition (46% or 54%), pneumonia alone was rare (10%), co-existence of pneumonia with wheeze (bronchospasm) was more frequent (22% or 15%) and often diagnoses not related to the respiratory system were documented (18% or 17%). All the subjects in whom a preceding history of cough was not elicited had non-respiratory illnesses. An audible wheeze was appreciated in only 44 of the 150 cases (29.3%) with an auscultable wheeze. The two alternatives represented a significant (p < 0.0001) improvement over the WHO algorithm preventing inappropriate usage of both antibiotics and bronchodilators, primarily by restricting over-prescription of the former (14% and 26.5% for proposed algorithms 1 and 2, respectively) and under-utilization of the latter (40%). The performance of the alternative algorithms for the radiologist-aided diagnosis was marginally better for over-prescription of antibiotics (16.2% and 30.9% for proposed algorithms 1 and 2, respectively). CONCLUSION: It is feasible to amalgamate simple clinical features (history of: (i) previous similar episode of cough and difficult breathing, and (ii) fever) in the WHO case management algorithm to significantly refine the antibiotic (95% CI range 7% to 33%) and bronchodilator (35%; 95% CI 27% to 43%) prescription.

Algorithms↗

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↗

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↗

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↗

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↗