Cosegregation of a novel homozygous CYP11B1 mutation with the phenotype of non-classical congenital adrenal hyperplasia in a consanguineous family.

We report a novel missense mutation of CYP11B1 causing non-classical 11beta-hydroxylase deficiency in 3 members of a consanguineous Turkish family. Two siblings presented with clinical evidence of precocious pseudopubarche. Biochemistry suggested 11beta-hydroxylase deficiency and genetic analysis revealed that they were homozygous for the missense mutation L489S within exon 9 of the CYP11B1 gene.

Cellular recognition of Mycobacterium tuberculosis ESAT-6 and KatG peptides in systemic sarcoidosis.

Sarcoidosis is an enigmatic disease with a pathology similar to that of tuberculosis. We detected Th-1 immune responses to Mycobacterium tuberculosis ESAT-6 and KatG peptides from peripheral blood mononuclear cells from 15/26 sarcoidosis, 1/24 purified-protein-derivative-negative (PPD-) (P < 0.0001, Fisher's exact test), and 7/8 PPD-positive (PPD+) subjects (P = 0.

Reactivation of systemic lupus erythematosus after initiation of highly active antiretroviral therapy for acquired immunodeficiency syndrome.

As the demographics of human immunodeficiency virus (HIV) infection continue to include more African-American and Hispanic females, the prevalence of concomitant HIV infection and systemic lupus erythematosus (SLE) may increase. We describe a 36-year-old woman with a 19-year history of active SLE who, after acquiring HIV infection, developed quiescent SLE with advanced immunosuppression (CD4 cell count 10/2%). After presenting with an opportunistic infection, she began receiving highly active antiretroviral therapy.

Mycobacterial antigens may be important in sarcoidosis pathogenesis.

Purpose Of Review: To describe the most recent epidemiologic, molecular and immunologic literature related to the role of infectious antigens in sarcoidosis pathogenesis, with a focus upon Mycobacterium and Proprionibacterium species.

Recent Findings: Recent studies of successful molecular analysis for and humoral immunity to mycobacterial antigens from sarcoidosis patients have renewed interest in a potential role of mycobacteria in sarcoidosis. One study provided molecular and immunologic evidence for mycobacteria among sarcoidosis subjects from the United States.

Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly.

Background: Vascular endothelial growth factor (VEGF) is involved in activation of the matrix metalloproteinase (MMP) system; the latter is implicated in atherosclerosis and cardiovascular disease. Patients with acromegaly have reduced life expectancy primarily due to cardiac disease.

Aim: This study assessed plasma MMPs and VEGF levels in patients with active acromegaly (IGF-I > 130% upper limit of normal), and on treatment with pegvisomant.

Growth hormone deficiency and replacement in patients with treated Cushing's Disease, prolactinomas and non-functioning pituitary adenomas: effects on body composition, glucose metabolism, lipid status and bone mineral density.

Background/aims: This study was designed to determine whether previous Cushing's disease (CD) or prolactinoma (PRL) could exert adverse effects additional to those of growth hormone (GH) deficiency as a consequence of variable degrees of prior hypogonadism or hypercatabolism. We report the effects of 5 years GH treatment in 124 GH deficiency adults; 42 patients with non-functioning pituitary adenomas (NFPA), 43 with treated PRL and 39 with treated CD.

Methods: Fasting plasma glucose, HbA(1c), lipoprotein profile, anthropometry and bone mineral density (BMD) were measured at baseline, 6 months and annually up to 5 years.

OntoDiagram: automatic diagram generation for congenital heart defects in pediatric cardiology.

In pediatric cardiology as well as many other medical specialties, the accurate portrayal of a large volume of patient information is crucial to providing good patient care. Our research aims at utilizing clinical and spatial ontologies representing the human heart, to automatically generate a Mullins-like diagram based on a patient's information in the cardiology databases. Our ontology allows an intuitive way of modeling congenital defects with the structure of the human heart.

Tissue plasminogen activator combined with human recombinant deoxyribonuclease is effective therapy for empyema in a rabbit model.

Objectives: There have been no controlled studies to test the efficacy of tissue plasminogen activator (tPA) or recombinant human deoxyribonuclease (rhDNase) in the treatment of empyema. In vitro studies show that streptokinase without rhDNase does not liquefy empyemic material from rabbits. However, the combination of streptokinase and streptodornase and rhDNase have been shown to liquefy pus in vitro.

Hypertension prevalence awareness, treatment and control in North Nashville.

North Nashville is a largely African-American community known to suffer from increased cardiovascular mortality compared with whites in the same area of Davidson County. The burden of hypertension, a well-known risk factor for cardiovascular death, has not been fully described for this population. To quantify the prevalence, awareness, treatment and control of hypertension in the North Nashville community, we screened 132 patients aged 18 and older at the 2005 Juneteenth festival on Jefferson Street.

Benefits of screening in von Hippel-Lindau disease--comparison of morbidity associated with initial tumours in affected parents and children.

Von Hippel-Lindau (VHL) is a rare autosomal dominant syndrome characterised by the association of retinal and CNS haemangioblastomas, phaeochromocytoma and renal cell carcinoma. If a child of an affected parent has inherited a VHL mutation or the parent's mutation cannot be identified, then clinical screening is recommended. We report the clinical features in three parent-offspring pairs where the parents have presented clinically with renal cell carcinoma, phaeochromocytoma, cerebellar haemangioblastoma and retinal haemangioma, and the children have undergone pre-symptomatic screening.

The management of differentiated thyroid cancer using 123I for imaging to assess the need for 131I therapy.

Background: Follow-up of 131I whole-body scanning after 131I ablation is associated with potential stunning. Previous studies have suggested that, for scanning, 123I is more sensitive than 131I in identifying thyroid tissue, but its specificity when positive is less certain.

Aim: The use of 123I as an imaging agent in place of serial 131I imaging has been evaluated in the surveillance and treatment of differentiated thyroid carcinoma.

Treatment of pituitary tumors: pegvisomant.

Pegvisomant is a pegylated analog of growth that functions as a growth hormone receptor antagonist. The drug is capable of normalizing serum IGF-I concentrations (the chief mediator of disease activity in acromegaly) in 97% of patients, and therapy is associated with significant improvements in the symptoms and signs of GH excess. Biochemical control may be achieved with pegvisomant in patients wholly or partially resistant to somatostatin analogs, and there are emerging data to suggest that the drug may be particularly suitable for patients with acromegaly and co-existent diabetes mellitus.

Tumour surveillance imaging in patients with extrapituitary tumours receiving growth hormone replacement.

Objective: GH replacement is widely used in the management of patients with adult-onset (AO)-GH deficiency (GHD). In most cases, AO-GHD arises as a result of pituitary/peripituitary tumours and/or their treatment, but the effect of GH replacement on recurrence/regrowth of these tumours is unknown. The aim of this study was to examine the effect of GH replacement in a group of patients with primary tumours of the parasellar region, many of which (e.

Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant.

Context: In clinical practice, patients with acromegaly may be switched from therapy with long-acting somatostatin analogs to pegvisomant. The effect of changing therapies on glucose homeostasis and safety has not been reported.

Objectives: The objectives of this study were to monitor changes in IGF-I levels, glycemic control, and safety, particularly liver function and tumor size.

Markers of cell proliferation in a GH-producing adenoma of a patient treated with pegvisomant.

We report our findings on markers of cell proliferation (Ki-67 labelling index and topoisomerase-alpha expression) in a somatotroph pituitary tumour before and after exposure to pegvisomant, a GH receptor antagonist developed for the treatment of acromegaly. Specimens from two separate pituitary operations, separated by a period of 17 years that included 4 years of pegvisomant treatment, were stained for markers of cellular proliferation. Ki-67 labelling index and topoisomerase-alpha expression were both markedly greater (1-3% compared with 0-0.

Clinical use of pegvisomant for the treatment of acromegaly.

Understanding the mechanisms by which growth hormone (GH) interacts with its receptor has led to the design of compounds that function as GH receptor antagonists. One such compound has been conjugated to polyethylene glycol (PEG) to produce a drug, pegvisomant, which has been extensively investigated as a treatment for acromegaly. It was recently approved for clinical use in the US and will shortly be available on prescription in Europe.

Disease activity in acromegaly may be assessed 6 weeks after discontinuation of pegvisomant.

Objective: Pegvisomant, a modified growth hormone (GH) molecule, is a novel medical therapy for acromegaly that functions as a GH receptor antagonist. Serum GH cannot be used as a marker of disease activity in patients taking this form of therapy, partly because GH levels rise on pegvisomant and partly because the drug cross-reacts with many routine GH assays. The purpose of this study was to assess the time for which it is necessary to discontinue pegvisomant prior to biochemical reassessment of acromegaly.

Vector projection of biomagnetic fields.

Biomagnetic measurements are increasingly popular as functional imaging techniques for the non-invasive assessment of electrically active tissue. Although most currently available magnetometers utilise only one component of the vector magnetic field, some studies have suggested the possibility of obtaining additional information from recordings of the full magnetic field vector. Three projection techniques were applied to different biomagnetic signals for analysis of the three orthogonal components of the vector magnetic field.

Transitional care of GH deficiency: when to stop GH therapy.

While the benefits of growth hormone (GH) therapy in adult hypopituitary patients with GH deficiency (GHD) are established, the role of continued GH therapy after final height in adolescent GH-deficient patients remains unclear. Preliminary data suggest that cessation of GH on completion of linear growth may be associated with impairment of somatic development and adverse changes in body composition. For the present time, the decision whether to continue GH treatment in adolescent patients with GHD is best made on an individual basis.

Comparison of continuation or cessation of growth hormone (GH) therapy on body composition and metabolic status in adolescents with severe GH deficiency at completion of linear growth.

Although GH replacement improves the features of GH deficiency (GHD) in adults, it has yet to be established whether cessation of GH at completion of childhood growth results in adverse consequences for the adolescent with GHD. Effects of continuation or cessation of GH on body composition, insulin sensitivity, and lipid levels were studied in 24 adolescents (13 males, 11 females, aged 17.0 +/- 0.

The place of pegvisomant in the acromegaly treatment algorithm.

The disfiguring disease acromegaly results from hypersecretion of growth hormone (GH). The main goals of treatment for acromegaly include normalisation of biochemical markers of disease activity to restore normal life expectancy, amelioration of signs and symptoms of the disease, removal of the pituitary tumour without damaging the optic chiasm and other peripituitary structures, and preservation of pituitary function. Conventional options for treatment of acromegaly include surgery, radiotherapy (RT), and medical therapy with either dopamine agonists or somatostatin (SMS) analogues.

Pegvisomant: a novel pharmacotherapy for the treatment of acromegaly.

Pegvisomant is a pegylated analogue of growth hormone (GH) that functions as a growth hormone receptor antagonist. Clinical trials of its use in acromegaly commenced in 1997; the drug was approved in the US in March 2003 and in Europe in November 2003. In the same year, it was made available on prescription in several European countries, with further launches due in 2004.

An investigation of the predictors of bone mineral density and response to therapy with alendronate in osteoporotic men.

Male osteoporosis is an important disease, with 25-30% of all hip fractures occurring in men. In a recent randomized, placebo-controlled study of osteoporotic males, alendronate 10 mg daily for 2 yr led to significant increments in bone mineral density (BMD), of a similar magnitude to those observed in postmenopausal women. In this study, specimens collected at intervals during the recent trial of alendronate in male osteoporosis, from 197 of the original 241 participants, were assayed for testosterone, estradiol, IGF-I, IGF binding protein 3 (IGFBP-3), bone-specific alkaline phosphatase [BSAP (serum)], and N-telopeptide of type I collagen corrected for creatinine [NTx (urine)].

Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant.

Aim And Method: Insulin resistance leading, in some cases, to glucose intolerance is an important contributory factor to the cardiovascular morbidity and mortality associated with acromegaly. The aim of this study was to document changes in insulin sensitivity (IS) in a group of seven patients with acromegaly (three male, four female, mean+/-s.d.