Harvey Kushner

• PhD
• CEO at BioMedical Computer Research Institute, Inc.

Objective: To evaluate satisfaction with segesterone acetate and ethinyl estradiol (SA/EE; 0.15 mg/0.013 mg) contraceptive vaginal system (CVS) use among women who had recently used contraceptive vaginal rings or contraceptive pills. The CVS is a ring-shaped contraceptive, used in a 21-days-in/7-days out regimen for up to 13 cycles and indicated fo...

Pathogenic germline variation in the microRNA processing gene DICER1 gives rise to an autosomal dominant, tumor‐predisposition disorder. Conditional deletion of Dicer1 in murine dental epithelium shows that it controls tooth patterning, size, number, and shape. The human dental phenotype of people with germline pathogenic variation in DICER1 is unk...

Purpose: Resident interview experiences are crucial for applicants when ranking programs. The purpose of the present study was to evaluate the interview experience among current oral and maxillofacial surgery (OMS) residents to determine the factors that influenced their selection and ranking of training programs and whether these experiences diff...

Fibrous dysplasia (FD) is a mosaic disease in which bone is replaced with fibro‐osseous tissue. Lesions expand during childhood, reaching final burden by age 15 years. In vitro data suggest that disease activity decreases in adulthood; however, there is no clinical data to support this concept. Bone turnover markers (BTMs) have been used as markers...

Background Patients with Psychotic Depression (PD) exhibit elevated cortisol levels. Competitively antagonizing cortisol at the glucocorticoid receptor (GR) with mifepristone demonstrated therapeutic benefit in early studies of patients with PD. We present a combined analysis of all controlled Phase 2/3 studies to report antipsychotic differences b...

Background: Psychotic depression has no Food and Drug Administration-approved treatment. Patients demonstrate significant dysregulation of the hypothalamic-pituitary-adrenal axis providing a biologically targeted treatment opportunity. The purpose of this study was to explore the clinical and biological effects of short-duration (7-day) glucocorti...

Objectives: To examine the effects of early low-dose androgen on motor, cognitive, and behavioral function in prepubertal boys with Klinefelter syndrome (47,XXY). Study design: Double-blind trial of 84 boys, ages 4-12 years, randomized to oxandrolone (Ox; 0.06 mg/kg daily; n = 43) or placebo (Pl; n = 41) for 24 months. Standardized assessments w...

Background: Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for pro...

Objective TX-004HR is an investigational, muco-adhesive, vaginal, softgel capsule containing low-dose, solubilized, 17β-estradiol designed to treat postmenopausal vulvar and vaginal atrophy (VVA) and improve user experience without an applicator and less mess. Methods As part of the 12-week, placebo-controlled, double-blind, phase 3 REJOICE trial...

Objective To evaluate the safety and efficacy of TX-004HR vaginal estradiol soft-gel capsules for moderate-to-severe dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Methods In this randomized, double-blind, placebo-controlled, phase 3 study, postmenopausal women with a self-identified most bothersome symptom of dyspareunia r...

Objective To evaluate the pharmacokinetics of TX-004HR vaginal estradiol softgel capsules when used for treating moderate-to-severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy. Methods A substudy of the REJOICE trial (multicenter, double-blind, placebo-controlled, phase 3) evaluated the pharmacokinetics of 4, 10, and 25-μg...

Lidocaine vaginal bioadhesive gel is being developed as a local anesthetic for use in minimally invasive outpatient gynecological procedures and was investigated in single-dose and multiple-dose studies in healthy, young, adult women. Lidocaine doses of 2.5, 5 and 10% (w/w) were administered and parent drug and metabolites, monoethylglycinexylidide...

Background: Polyostotic fibrous dysplasia is a skeletal disease that results from somatic activating mutations in the gene GNAS in skeletal stem cells, leading to proliferation of immature osteogenic cells with replacement of normal marrow and bone with fibro-osseous tissue. Lesions may cause bone deformity or fracture. In the surgical care of pol...

Purpose: Orthognathic surgery can induce changes in airway volume. The aim of this study was to determine whether there is a correlation of surgical movement of the maxilla or mandible to airway volume changes. Materials and methods: This was a prospective cohort study and the sample was composed of patients undergoing single-jaw orthognathic pr...

Background: Overweight and obesity are common among patients with Cushing's syndrome (CS) and may persist in some patients even after ostensibly curative surgery, contributing to cardiometabolic dysfunction and increased cardiovascular risk. Mifepristone, a selective glucocorticoid receptor antagonist, was effective in controlling hyperglycemia in...

To examine the relationship between dose, clinical response (based on independent evaluation of metabolic, physical, neurological, and social assessments), and safety of mifepristone treatment in patients with endogenous Cushing's syndrome (CS). This post-hoc analysis included 40 clinical responders and 50 participants who received a dose of mifepr...

To examine and compare the skeletal and dental effects of surgically assisted rapid palatal expansion (SARPE) and multipiece Le Fort osteotomy using cone-beam computed tomography (CBCT). This was a prospective cohort study. Patients underwent SARPE or multipiece Le Fort I osteotomy to address maxillary transverse deficiency. CBCT scans were taken p...

Context: Fibrous dysplasia (FD) is a rare skeletal disorder, resulting in deformity, fracture, functional impairment, and pain. Bisphosphonates have been advocated as a potential treatment. Objective: To determine the efficacy of alendronate for treatment of FD. Design: Two-year randomized, double-blind, placebo-controlled trial. Setting: Cl...

Fibrous dysplasia (FD) is a benign skeletal disease caused by activating mutations of Gsα. These mutations lead to formation of abnormal and mechanically unsound bone and fibrotic tissue. Clinical sequelae include deformity, fracture, and pain. Studies in bisphosphonates have shown improvement in bone pain and inconsistent effects on FD mineralizat...

Collagenase Clostridium histolyticum (CCH) injection is a nonoperative treatment of hand contractures from Dupuytren disease. This study assessed the efficacy and safety of CCH in several subgroups of patients with increased surgical risk.Data were pooled from 3 randomized, placebo-controlled, double-blind trials. This analysis included 271 patient...

Background: Testosterone decline becomes more prevalent as men age and symptomatic testosterone deficiency is associated with potentially serious comorbidities. Despite limitations, registries can provide an opportunity to accumulate data regarding disease management in a typical patient population, including diagnosis, treatment, and outcomes. M...

Background: Although hypogonadism is common in men with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), testosterone levels after testosterone replacement therapy (TRT) in this population have not been reported. Methods: The Testim Registry in the United States (TRiUS) was the first prospective, observational regist...

Purpose: The JOINT I (United States) and JOINT II (Australia and Europe) studies evaluated the efficacy and safety of collagenase clostridium histolyticum (CCH) injection for the treatment of Dupuytren contracture. Methods: Both studies used identical open-label protocols. Patients with fixed-flexion contractures of metacarpophalangeal (MCP) (20...

Testosterone levels naturally decline with age in men, often resulting in testosterone deficiency (hypogonadism). However, few studies have examined hypogonadal characteristics and treatment in older (≥65 years) men. To compare data at baseline and after 12 months of testosterone replacement therapy (TRT) in hypogonadal men ≥65 vs <65 years old. Da...

Collagenase Clostridium histolyticum (CCH) is a non-surgical, efficacious therapy for Dupuytren's contracture (DC). This study evaluated the efficacy and safety of CCH in patients with previous DC surgery. Data from 12 CCH clinical trials were pooled. At screening, patients provided details about the type/date of previous DC surgery. Reviewers code...

Among patients with hypogonadism-associated comorbidities, opioid users have the highest incidence of hypogonadism. Data from the Testim Registry in the United States were analyzed to determine the efficacy of testosterone replacement therapy in opioid users vs nonusers. Prospective, 12-month observational cohort registry. Hypogonadal men (N = 849)...

To contrast the behavioral and social phenotypes including a screen for autistic behaviors in boys with 47,XYY syndrome (XYY) or 47,XXY Klinefelter syndrome (KS) and controls and investigate the effect of prenatal diagnosis on the phenotype. Patients included 26 boys with 47,XYY, 82 boys with KS, and 50 control boys (ages 4-15 years). Participants...

To determine the effect of long-term testosterone replacement therapy (TRT) on depression symptoms in hypogonadal men. Data were from TRiUS, a multicenter, 12-month observational registry (N = 849) of hypogonadal men prescribed 1% testosterone gel. Measures including total testosterone (TT) were assessed at baseline and months 3, 6, and 12. Depress...

Abstract Background Recent evidence suggests that there may be a bidirectional, physiological link between hypogonadism and metabolic syndrome (MetS), and testosterone replacement therapy (TRT) has been shown to improve some symptoms of MetS in small patient populations. We examined the effect of 12 months of TRT on MetS components in a large cohor...

We measured prostate specific antigen after 12 months of testosterone replacement therapy in hypogonadal men. Data were collected from the TRiUS (Testim® Registry in the United States), an observational registry of hypogonadal men on testosterone replacement therapy (849). Participants were Testim naïve, had no prostate cancer and received 5 to 10...

Up to 30% of erectile dysfunction (ED) patients treated with phosphodiesterase type 5 (PDE5) inhibitors do not show improved sexual function, which may be due in part to low serum testosterone. Hypogonadal patients already receiving testosterone replacement therapy (TRT) likewise can still suffer from symptoms of sexual dysfunction. In these patien...

The aim of this study was to determine whether there are differences in esthetic preferences and orthognathic treatment for Asian patients between US- and Asian-trained surgeons. Twenty-five Caucasian-American, 23 Asian-American, 24 Asian oral and maxillofacial surgeons (OMFS) completed an Institutional Review Board (IRB)-approved survey. They were...

Testosterone deficiency (TD) is prevalent among men seeking medical attention and may be associated with other comorbidities. The Testim(®) Registry in the United States (TRiUS), a large, multicenter, prospective, 12-month observational cohort registry, was established to quantify symptoms and comorbidities of hypogonadal men in real-world clinical...

Untreated girls with Turner syndrome (TS) have growth failure, and adult height is, on average, 20 cm less than predicted height. Treatment with growth hormone (GH) is now standard of care. The objective of this study was to investigate the benefit of adding oxandrolone (Ox) to GH in a long-term, randomized, placebo (Pl)-controlled prospective tria...

Purpose: We measured prostate specific antigen after 12 months of testosterone replacement therapy in hypogonadal men. Materials and Methods: Data were collected from the TRiUS (Testim® Registry in the United States), an observational registry of hypogonadal men on testosterone replacement therapy (849). Participants were Testim naïve, had no prost...

Objective: To determine the effect of long-term testosterone replacement therapy (TRT) on depression symptoms in hypogonadal men. Methods: Data were from TRiUS, a multicenter, 12-month observational registry (N = 849) of hypogonadal men prescribed 1% testosterone gel. Measures including total testosterone (TT) were assessed at baseline and months 3...

: Patients with oral premalignant lesions (OPL) present with oral squamous cell carcinomas (OSCC) at a much higher rate than the general population. There are currently no useful markers that indicate specifically which OPLs are most likely to progress. Three small integrin binding ligands N-linked glycoprotein (SIBLING) family proteins, bone sialo...

To study androgen treatment effects on arithmetic performance in girls with Turner syndrome. Forty-four girls, ages 10 to 14 years at baseline, completed 4 years of treatment with oxandrolone (Ox) or placebo (Pl). All received growth hormone and estrogen replacement therapy. We assessed the number of girls with severe learning disability (LD, stand...

Insulin resistance has been linked to the development of type 2 diabetes mellitus and increased cardiovascular risk in several high-risk populations. The purpose of this study was to determine if insulin resistance measured by insulin clamp can predict deterioration of glucose metabolism and increased cardiovascular risk in nondiabetic young adult...

The disposition index, the product of the insulin sensitivity index (S(I)) and the acute insulin response to glucose, is linked in African Americans to chromosome 11q. This link was determined with S(I) calculated with the nonlinear regression approach to the minimal model and data from the reduced-sample insulin-modified frequently-sampled intrave...

The goal of this study was to contrast the cognitive phenotypes in boys with 47,XYY (XYY) karyotype and boys with 47,XXY karyotype [Klinefelter syndrome, (KS)], who share an extra copy of the X-Y pseudoautosomal region but differ in their dosage of strictly sex-linked genes. Neuropsychological evaluation of general cognitive ability, language, memo...

While national mortality rates for end-stage renal disease (ESRD) patients remain high, for the past 4 years, lower than expected local mortality rates have been consistently seen in our facilities. Because of these progressive improvements in mortality rates, a study of 687 hemodialysis patients over a 4-year period, 2003 through 2006, was underta...

The neurocognitive phenotype of Turner syndrome (TS) includes deficits in social cognitive skills such as recognition of the facial affect expressing fear. A TS social cognition locus was previously mapped to a 5 megabase interval of Xp11.3-p11.4 by Good et al. 2003. A recent study by these same workers found evidence for association of a SNP in th...

Total body size and central fat distribution are important determinants of insulin resistance. The BMI and waist circumference (WC) thresholds in African Americans that best predict insulin resistance are unknown. Our goal was to determine the BMI and WC values in African Americans, which optimally predict insulin resistance. The subjects were Afri...

The goal of this study was to expand the description of the cognitive development phenotype in boys with Klinefelter syndrome (47,XXY). We tested neuropsychological measures of memory, attention, visual-spatial abilities, visual-motor skills, and language. We examined the influence of age, handedness, genetic aspects (parental origin of the extra X...

Insulin resistance is a risk factor for cardiovascular disease. Therapies to lower blood pressure should not decrease insulin sensitivity, especially among high-risk patients such as diabetics. This study examined the effect of the beta1-selective adrenergic receptor-blocking agent extended-release metoprolol succinate (ER metoprolol) on insulin se...

This study investigated the role of relative androgen excess, designated by low sex hormone-binding globulin (SHBG), on development of type 2 diabetes in premenopausal African American women. A prospective, longitudinal study was conducted on premenopausal African American women, initially aged 36 to 43 years (n=119). Patients were reexamined 8 yea...

Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy. Fibrous dysplasia of bone (FD) is an uncommon skeletal dis...

Despite higher rates of cardiovascular disease, African Americans have a more favorable lipid profile. The purpose of the study was to examine the association between plasma lipid concentrations and insulin resistance in African Americans and to determine if insulin resistance is present at a lower triglyceride (TG) threshold than is used for metab...

Turner syndrome (TS) is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls...

Insulin resistance is a risk factor for cardiovascular disease. Therapies to lower blood pressure should not decrease insulin sensitivity. Some b-adrenergic blocking agents can have an adverse effect on insulin sensitivity. This study examined the effect of extended-release metoprolol succinate on insulin sensitivity. Nondiabetics with hypertension...

Polyostotic fibrous dysplasia has a wide clinical spectrum, with substantial variation between patients in terms of orthopaedic manifestations, including the number of fractures, the degree of deformity of the limbs, and the presence of scoliosis. Data from bone scans, skeletal surveys, and records were correlated with the Pediatric Outcomes Data C...

Treatment of prediabetes attenuates progression to type 2 diabetes mellitus. The American Diabetes Association (ADA) previously defined prediabetes as either impaired fasting glucose (IFG) = 6.1 to 6.9 mmol/L (110-125 mg/dL) and/or impaired glucose tolerance (IGT) (2-hour postload glucose of 7.8-11.0 mmol/L [140-199 mg/dL]). For practical reasons,...

The erythropoietic-stimulating hormone, darbepoetin alfa (Aranesp; DPO; Amgen, Thousand Oaks, California) is a long-acting agent growing in popularity as the preferred anemia management agent for patients with chronic kidney disease. Use of this drug in existing patients treated with rHu-EPO (epoetin alfa; EPO) requires conversion dosing and the po...

Fibrous dysplasia of bone (FD) is a congenital, non-heritable skeletal disorder that is associated with multiple skeletal complications, including repeated fractures, limb length discrepancy, and bone pain. The disease-specific impact of FD on quality of life outcomes is unknown. We sought to understand the impact of the scope and extent of the ske...

An instrument to measure skeletal burden in fibrous dysplasia was developed. Biological and clinical relevance was shown by correlating skeletal burden scores with bone markers, quality of life, and ambulatory status. Childhood scores predict adult ambulatory status, and scores were unaffected when bone markers decreased with bisphosphonate treatme...

The purpose of this study was to determine which measures obtained from an oral glucose tolerance test (OGTT) are the best estimates of insulin sensitivity measured directly using the euglycemic hyperinsulinemic clamp procedure. Data were examined from a study conducted on 307 young adult African-American men and women. An OGTT with insulin measure...

The high prevalence of insulin resistance syndrome in African Americans predisposes this population to higher morbidity and mortality from cardiovascular disease. To test the hypothesis that the combination of obesity and high blood pressure (BP) represents the physical phenotype of insulin resistance syndrome, 337 African-American men and women ag...

Premature ovarian failure (POF) is generally defined as amenorrhea, hypoestrogenism, and elevated gonadotropins occurring in a woman before the age of 40 yr. Usually, the etiology is unknown. Turner syndrome (TS, monosomy X), also associated with ovarian failure, has a characteristic neurocognitive profile. TS females, as a group, have specific def...

Unlabelled: In patients with polyostotic fibrous dysplasia of bone, the peak incidence of fractures is during the first decade of life, followed by a decrease thereafter. Phosphaturia is associated with an earlier incidence and increased frequency of fractures. Introduction: Fibrous dysplasia (FD) is a disorder involving either one (monostotic)...

The fetal programming theory that birth weight contributes to blood pressure or body size in later life is examined in this study. A prospective longitudinal study was conducted on subjects who were examined as newborns and prospectively interviewed and re-examined at 11 to 14 years old. Low birth weight (<2500 g) was present in 36% of the sample....

Fibrous dysplasia (FD) is a rare skeletal disease caused by activating GNAS1 gene mutations often found in association with the McCune-Albright syndrome (MAS). Multiple bones may be affected in FD, including maxilla and mandible. Patients with MAS have different endocrinopathies that can further influence bone metabolism. The purposes of this cross...

An association of plasma homocysteine concentration ([Hcy]) with cardiovascular events has been described, but the role of [Hcy] in the early phase of cardiovascular disease is uncertain. The purpose of this study was to determine whether [Hcy] is related to blood pressure (BP) or other risk factors in African Americans, a population at high risk f...

Am J Hypertens (2003) 16, 236A–237A; doi:10.1016/S0895-7061(03)00721-0 P-548: Effect of birth weight on blood pressure in early adolescence Bonita Falkner1, Sonia Hulman1, Barbara Scollon1, Mary Curry1 and Harvey Kushner11Division of Nephrology, Thomas Jefferson University, Philadelphia, PA; Division of Neonatology, Crozer-Keystone Health System,...

Reference BP values are based on measurement methodology of Hg column sphygnomanometry. Due to possible environmental toxicity from Hg, the Hg column instruments for measuring BP are becoming unavailable. The accuracy of alternative instruments for measurement of BP is unresolved. The purpose of this study was to compare, in children, BP measuremen...

Turner syndrome (TS) represents a unique, sex hormone-deficient model in which to study the biological effects of androgen treatment (replacement) on cognition in females because TS girls have gonadal dysgenesis and absent ovarian androgen and estrogen production. We investigated the effects of androgen replacement therapy in TS girls, ages 10-14 y...

The purpose of this investigation was to examine the theory that low birth weight, as a marker of intrauterine environment, is a determinant of higher blood pressure in later life. A prospective longitudinal study was conducted in which a sample (N=250) of subjects that were examined in the newborn period, were re-examined at age 12-14 years. Low b...

Fibrous dysplasia of bone frequently involves the anterior base of the cranium and results in encasement of the optic-nerve canals. It has been assumed that such encasement leads to constriction and eventual blindness. There is controversy about whether patients should be regularly monitored or whether they should undergo prophylactic decompression...

McCune-Albright syndrome (MAS) is a disorder characterized by the triad of café-au-lait skin pigmentation, polyostotic fibrous dysplasia of bone, and hyperfunctioning endocrinopathies, including GH excess. The molecular etiology of the disease is postzygotic activating mutations of the GNAS1 gene product, G(s)alpha. The term gsp oncogene has been a...