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Seema Kumar

Publications and source records attributed to Seema Kumar.

11 recordsLinked to original sources
PubMed2026

Streamlining Diagnosis of Bardet-Biedl Syndrome: New Diagnostic Algorithm With Updated Criteria.

Considerable advances have been made in our understanding of Bardet-Biedl syndrome (BBS), particularly in its core clinical features and molecular genetics, warranting an update to the existing diagnostic criteria framework. Using a rigorous, evidence-based, and consensus-driven process, a multidisciplinary group of international experts and patient-led organizations developed an updated diagnostic algorithm. This algorithm provides practical, updated guidance for clinicians, including a pathway for accurately incorporating genetic findings into the diagnostic process. We recommend that a clinical diagnosis requires either 4 major criteria or 3 major and 2 minor criteria. Revised major criteria are retinal dystrophy, obesity (or overweight in individuals <&#x2009;2&#x2009;years old), congenital anomalies of the kidney and urinary tract or chronic kidney disease, hypogonadism/genital anomalies, neurodevelopmental/neurocognitive manifestations, and postaxial polydactyly. The diagnosis can also be established with a positive genetic testing result in patients exhibiting &#x2265;&#x2009;1 major criterion, provided that genetic findings should be interpreted in the context of the patient's clinical presentation, age, family history, and overlap with related ciliopathies. These consensus criteria offer a simple algorithm incorporating updated definitions for major and minor criteria and genetic testing to support a timely and accurate diagnosis of patients with BBS, inform genetic counseling, and potentially facilitate earlier access to treatment. Trial Registration: CRIBBS Registry; ClinicalTrials.gov: NCT02329210.

Humans↗
PubMed2006

Surgical management of Graves disease in childhood and adolescence: an institutional experience.

BACKGROUND: Graves disease is the most common cause of hyperthyroidism in children. Medical therapy, radioiodine ablation, and thyroidectomy are all treatment options. To evaluate the safety and efficacy of operative therapy, we updated our operative experience with pediatric Graves disease at a single tertiary care center. METHODS: The medical records of children <18 years old who underwent thyroidectomy for Graves disease between 1986-2003 were reviewed. RESULTS: We identified 78 patients (median age, 13.8 years; 87% female). The most common presenting signs and symptoms included heat intolerance (61%), decreased academic performance (50%), tremor (49%), and ophthalmopathy (43%). All patients had clinical and laboratory evidence of autoimmune thyrotoxicosis. Sixty-nine percent chose operative therapy because of failure of medical therapy or adverse drug reactions. Near-total thyroidectomy was the most common surgical procedure performed (65%). Pathology demonstrated previously unrecognized thyroid malignancies in 4 (5%) patients. Operative morbidities were transient and included hypoparathyroidism (6%) and recurrent laryngeal nerve neuropraxia (1%). Three (4%) patients who underwent subtotal thyroidectomy developed recurrent hyperthyroidism; all were treated successfully with radioiodine ablation. Of patients presenting with ophthalmopathy, 85% noted improvement postoperatively, while 1 (3%) patient experienced worsening of symptoms. Only 5% developed new-onset Graves ophthalmopathy after operation. CONCLUSIONS: Near-total thyroidectomy for Graves disease in children is safe and effective when performed by experienced thyroid surgeons. In addition to relief of systemic symptoms, the majority of patients presenting with Graves ophthalmopathy experienced improvement of their ocular disease after operation. In 5% of patients, surgical management allowed for detection and treatment of clinically occult thyroid malignancies.

Adolescent↗
PubMed2005

Gene expression profiling of orbital adipose tissue from patients with Graves' ophthalmopathy: a potential role for secreted frizzled-related protein-1 in orbital adipogenesis.

CONTEXT: The signs and symptoms of Graves' ophthalmopathy (GO) result from inflammation and increased volume of the orbital adipose tissues and extraocular muscles. OBJECTIVE: Our objective was to identify differentially regulated genes that may be involved in stimulating the orbital adipose tissue expansion seen in GO. DESIGN: Gene expression profiling was used to compare genes expressed in orbital adipose tissues from GO patients and normal individuals. SETTING: The study took place at a private practice tertiary referral center. PATIENTS: Orbital adipose tissues were collected at transantral orbital decompression surgery from 20 euthyroid patients undergoing this procedure for severe GO and at early autopsy from eight normal individuals having no evidence of thyroid or ocular disease. RESULTS: Of the 12,686 genes analyzed, 25 known genes were increased in expression (>4-fold) in GO orbital tissues, whereas 11 genes were decreased (>4-fold). Up-regulated genes, confirmed by quantitative RT-PCR, included secreted frizzled-related protein-1 (sFRP-1; 18.5-fold) and several adipocyte-related genes, including peroxisome proliferator activated receptor-gamma (44.1-fold) and adiponectin (25-fold). Treatment in vitro of GO orbital preadipocytes with recombinant sFRP-1 (100 nm) significantly increased adiponectin (2.0-fold; P < 0.05), leptin (7-fold; P < 0.002), and TSH receptor mRNA (13-fold; P < 0.003) levels and enhanced Oil red-O staining in the cultures. CONCLUSIONS: These results support the concept that orbital adipogenesis is enhanced in GO and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process.

Adipocytes↗
PubMed2004

Evidence for enhanced adipogenesis in the orbits of patients with Graves' ophthalmopathy.

The signs and symptoms of Graves' ophthalmopathy (GO) result from increased volume of the orbital contents, including adipose, connective, and extraocular muscle tissues. We wanted to determine whether the expanded adipose tissue volume might be in part attributable to de novo adipogenesis. We measured levels of mRNA encoding leptin, adiponectin, peroxisome proliferator-activated receptor gamma (PPAR gamma), preadipocyte factor-1, and TSH receptor (TSHr) genes in orbital adipose tissues from GO patients (n = 22) and normal individuals (n = 18) and in orbital preadipocyte cultures derived from GO patients (n = 6) and normal subjects (n = 3) using quantitative real-time RT PCR. We found increased leptin, adiponectin, PPAR gamma, and TSHr expression in GO compared with normal orbital tissue samples, with positive correlations in the GO tissues between TSHr and leptin, adiponectin and PPAR gamma. In vitro differentiation of GO and normal preadipocytes resulted in enhanced adiponectin, leptin, and TSHr expression, with greater expression of the latter two genes in the GO cultures. These results suggest that de novo adipogenesis within orbital tissues with parallel enhanced expression of TSHr may be important in the pathogenesis of GO, and that potential therapies for GO might include inhibition of the adipogenic pathway.

Adipocytes↗
PubMed2004

Cushing's syndrome after intra-articular and intradermal administration of triamcinolone acetonide in three pediatric patients.

BACKGROUND: Intra-articular and intradermal steroids are often used for their antiinflammatory effect. There is limited experience with intra-articular and intralesional administration of corticosteroids in the pediatric age group. DESIGN/METHODS: We performed a retrospective chart review of 3 pediatric patients who developed Cushing's syndrome after local administration of triamcinolone acetonide (TCA). RESULTS: Two females 9 and 17 years old, received intra-articular injections of TCA. One patient received multiple injections of TCA into the interphalangeal joints (cumulative dose: 120 mg), whereas the other received a single injection of 40 mg, a dose that is considered to be in the therapeutic range, into the hip joint. The third patient, a 7-year-old female, received multiple intralesional injections of TCA. These patients developed signs and symptoms of hypercortisolism that appeared 4 to 6 weeks after local administration of TCA and lasted for 4 to 6 months after the last dose of TCA. TCA was detectable in the plasma and urine by the liquid chromatography/tandem mass spectrometry method 4 to 5 months after the last dose of the steroid. CONCLUSIONS: We noted evidence for Cushing's syndrome in 3 pediatric patients after intra-articular or intradermal administration of TCA. One of them had received a therapeutic dose of TCA. The possibility of hypothalamic-pituitary-adrenal axis suppression should be considered in patients who have received intra-articular or intradermal steroid injections, particularly in those who have had multiple or relatively high doses.

Adolescent↗
PubMed2003

Generation of a monoclonal antibody that blocks epithelial binding of unopsonized particles.

Alveolar macrophages (AMs) and epithelial cells (ECs) are the first cells in the lung to encounter inhaled environmental particles. The initial interaction between AMs and particles is mediated by specific scavenger receptors, but the nature of the structure(s) on ECs that also bind particles has not been well-described. To characterize the nature of the EC particle receptor, we screened a panel of mouse anti-human EC hybridomas for functional blockade of EC particle binding. This strategy identified a monoclonal antibody (MAb) (EPR1) that blocks binding of titanium dioxide (TiO(2)) particles to the EC line which served as the immunogen (A549), as well as to other EC lines (Beas 2-B, HTB54, HeLa, and MDA-MB-435S). EPR1 demonstrated specific labeling of ECs using immunohistology techniques and its expression could be quantitated by flow cytometry of permeabilized ECs in suspension. MAbs such as EPR1 may prove useful in further analysis of receptors for inhaled particles on lung epithelial cells.

Animals↗
PubMed2003

Relative overexpression of macrophage-derived cytokines in orbital adipose tissue from patients with graves' ophthalmopathy.

Graves' ophthalmopathy (GO) is an autoimmune disorder involving the adipose and connective tissues of the orbit. The study of cytokines present in these tissues may reveal the nature of the cells and immune responses involved in GO pathogenesis. In the current study, we performed relative quantification of the expression of cytokine genes in orbital adipose tissue from patients with GO (n = 6) and normal individuals (n = 2). Real-time RT-PCR was performed using fluorescent probes and primers for cytokines including IL-1 beta, IL-2, IL-4, IL-5, IL-8, IL-10, IFN-gamma, and TNF-alpha. Results showed IL-1 beta to be the gene having the greatest fold expression increase over normal in four of six patients. TNF-alpha was increased in all six GO patients. In addition, IL-8, IL-10, and IFN-gamma were increased in five of six GO patients. We found no evidence of either IL-4 or IL-5 expression in any of the GO or normal samples. The increased expression of the macrophage-derived cytokines IL-1 beta, TNF-alpha, and IL-10 suggests the presence of macrophage activation and ongoing antigen presentation within the orbit in GO. In addition, the overexpression of IFN-gamma, without evidence of IL-4 or IL-5 expression, supports the concept that cell-mediated, rather than humoral, immunity plays the predominant role in pathogenesis of this disorder.

Adipose Tissue↗