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Biomedical subjects

R E Weiss

Publications and source records attributed to R E Weiss.

At least 19 recordsLinked to original sources
PubMed2006

A case of ACTH-independent bilateral macronodular adrenal hyperplasia and severe congestive heart failure.

Cortisol secretion in ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH) can be regulated by aberrant adrenal receptors. We describe a patient with Cushing's syndrome (CS) due to AIMAH and concomitant Class IV congestive heart failure (CHF). Clinical testing for the presence of aberrant receptors revealed a pronounced serum cortisol (257%) and aldosterone response (212%) to the administration of ACTH and a partial serum cortisol (35%) and aldosterone (106%) response to upright posture. This suggested the possible presence of aberrant hormone receptors for ACTH [melanocortin 2 receptor (MC2-R)], vasopressin, catecholamines or angiotensin II (AT-II) on the patient's adrenal glands. Adrenal tissue from the patient demonstrated an eight-fold increased expression of MC2-R compared to normal adrenal tissue. This increased expression was consistent with the increase in cortisol and aldosterone seen in response to exogenous ACTH. We propose that the severe CHF resulted in activation of the renin-angiotensin system, with an increased production of AT-II. The elevated circulating levels of AT-II may have led to increased expression of MC2-R on the patient's adrenal glands and increased responsiveness to ACTH. This unusual case of CS may elucidate a heretofore unknown mechanism for the development of AIMAH.

Adrenal Glands↗
PubMed2005

Resistance to thyroid hormone associated with autoimmune thyroid disease in a Turkish family.

The syndrome of resistance to thyroid hormone (RTH) is characterized by impaired tissue responses to thyroid hormone. Hashimoto's thyroiditis is the most common thyroid autoimmune disease. We present a Turkish family with both RTH and Hashimoto's thyroiditis. RTH was detected through the presence of point mutation in thyroid hormone receptor (TR), and Hashimoto's thyroiditis was diagnosed due to the presence of thyroid autoantibodies. The proposita, her affected mother as well as her unaffected sister have thyroid autoantibodies consistent with Hashimoto's thyroiditis, and a heterozygous point mutation in exon 10 encoding the ligand (3,3',5-L-T3)-binding domain of the TRbeta gene was detected in both the proposita and the mother. The mutation is a replacement of cytosine for guanine in codon 453 (CCT->GCT) producing a missense mutation substituting a normal proline with an alanine (P453A), which reduces the affinity for T3 to 17% of that of the normal TRbeta. Both also have modest elevation of serum TSH levels. In severe RTH, marked elevation of thyroid hormone concentrations in the absence of suppressed TSH supports the laboratory diagnosis of RTH. However, when RTH is mild and associated with thyroiditis, even a modest thyroid gland insufficiency can obliterate the serum T4 and T3 elevations, typical of RTH. This will manifest as elevated serum TSH. Demonstration of TRbeta gene mutation is then necessary to establish the diagnosis. In addition, under these circumstances, treatment with thyroid hormone should be considered.

Adolescent↗
PubMed2004

A novel splice variant involving the 5' untranslated region of thyroid hormone receptor beta1 (TRbeta1).

The thyroid hormone receptor beta (TRbeta) gene generates two different proteins by use of a different promoter (beta1 and beta2). We now report a novel short TRbeta1 RNA splice variant in humans lacking 35 nucleotides at the 3' end of the non-coding exon 1 due to an alternative 5' splice donor site. This short variant was first identified in sequences of cDNA obtained from cultured human fibroblasts. Both variants were found in human fibroblasts, brain, pituitary, adrenal gland, placenta, muscle, thyroid and lymphocytes. These TRbeta1 variants possess splice donor sites with a sequence score slightly favoring the TRbeta1 long variant. Variant-specific real-time polymerase chain reaction (PCR) showed that their relative proportions were equal except in pituitary and muscle, in which the long form was 3- and 5-fold in excess. T3 treatment of fibroblasts grown in thyroid hormone depleted medium did not affect the absolute or relative expression of the two variants. Furthermore, the expression level in fibroblasts from patients with resistance to thyroid hormone with or without TRbeta gene mutations was not different to that in fibroblasts from normal controls.

5' Untranslated Regions↗
PubMed2002

Circadian variation in Cushing's disease and pseudo-Cushing states by analysis of F and ACTH pulsatility.

Distinguishing pituitary-dependent Cushing's disease from pseudo-Cushing's states can present a diagnostic challenge. Although many studies potentially discriminate between the 2, only the dexamethasone-suppressed corticotropin-releasing hormone (CRF) stimulation test at 15 minutes is 100% sensitive or specific. We measured baseline profiles of F and ACTH in 31 Cushing's disease patients, 11 with pseudo-Cushing's and 17 controls. Venous blood was collected at 30 minute intervals for 24-h. Subjects also had CRF stimulation tests and 2.0 mg/day dexamethasone suppression tests. F and ACTH profiles were analyzed for circadian rhythmicity, variability, and pulsatility. Relative circadian amplitude was decreased in Cushing's disease compared to both pseudo-Cushing's and normal states. Relative pulse amplitude was reduced in Cushing's disease. Because of this dampening of circadian and pulsatile variations, the overall variability of F and ACTH levels around their mean levels as quantified by the intra-series coefficient of variation (CV), was also decreased in Cushing's disease compared to pseudo-Cushing's and normal states. A F 24-h CV<40% was able to distinguish Cushing's disease from pseudo-Cushing's with 100% sensitivity (95% confidence interval (CI), 88-100%) and specificity (CI, 71-100%). An ACTH CV<40% had 97% sensitivity (CI, 83-100%) and 100% specificity (CI, 71-100%). An overnight 8-h F CV <40% also distinguished Cushing's disease from pseudo-Cushing's with 100% sensitivity (CI, 88-100%) and specificity (CI, 71-100%). These data show that a simple index of total temporal variability (the intra-series CV) derived from the analysis of basal F profiles, provides a useful method to distinguish Cushing's disease from pseudo-Cushing's. A F or ACTH CV <40% discriminates Cushing's disease from pseudo-Cushing's and reflects reduced circadian and pulsatile variations.

Adolescent↗
PubMed2002

Risperidone-induced priapism.

Priapism is well documented as a potential side effect of psychotropic medications. To date, there have been no reports of risperidone-induced priapism in the urologic literature. We report a case of risperidone-induced priapism requiring surgical treatment.

Antipsychotic Agents↗
PubMed2002

Thyroid function and effect of aging in combined hetero/homozygous mice deficient in thyroid hormone receptors alpha and beta genes.

The maintenance of thyroid hormone (TH) homeostasis is dependent on the synthesis and secretion of TH regulated by TSH. This is achieved, in turn, by the negative feedback of TH on TSH secretion and synthesis, which requires the interaction with TH receptors (TRs). Derived by alternative splicing of two gene transcription products, three TRs (TRbeta1, TRbeta2 and TRalpha1) interact with TH while another, TRalpha2, binds to DNA but not to TH. In this study we compare the results of thyroid function tests in mice with deletions of the TRalpha and TRbeta genes alone and present novel data on mice that are double homozygous and combined heterozygous. Homozygous deletions of both the TRalpha and TRbeta in the same mouse (TRalphao/o; TRbeta-/-) resulted in serum TSH values only slightly lower than those in athyreotic, Pax8 knockout mice. Whereas the absence of TRalpha alone does not cause resistance to TH, the absence of TRbeta in the presence of TRalpha results in a 205, 169, 544% increase in serum thyroxine (T(4)), triiodothyronine (T(3)) and TSH concentrations respectively. However, in the absence of TRbeta, loss of one TRalpha allele can worsen the resistance to TH with a 243 and 307% increase in T(4) and T(3) respectively. Similarly, while the heterozygous mouse with a single TRbeta allele shows no alteration in thyroid function, the concomitant deletion of TRalpha brings about mild but significant resistance to TH. Furthermore, the severity of the resistance to TH was noted to decrease with age in parallel with the decrease in serum free T(4) values also seen in wild-type mice. These results demonstrate that (1) unliganded TRalpha or TRbeta are not absolutely necessary for the upregulation of TSH; (2) TRbeta but not TRalpha is sufficient for TH-mediated downregulation of TSH; and (3) TRalpha may partially substitute for TRbeta in mediating a partial TH-dependent TSH suppression.

Aging↗
PubMed2001

Estimation for paired binomial data with application to radiation therapy.

We compare and contrast several different methods for estimating the effect of treatment when responses are paired binomial observations. The ratio of binomial probabilities is the parameter of interest, while the binomial probabilities are nuisance parameters which may vary between pairs. The application is a meta-analysis of the treatment of rectal cancer, with observations in each study indicating the number of recurrences of the cancer in each of two groups, one with radiation therapy and one without. The ratio of the probabilities of recurrence in the radiation to non-radiation groups is of substantive interest, and is modelled as a logistic or complementary log-log function of an unknown linear combination of the covariates. The three methods we consider are maximum likelihood, a Bayesian approach and an approach based on estimating equations. For the MLE and Bayesian approach the potentially large number of nuisance parameters are estimated together with the parameters of interest, whereas for the estimating equation approach only the parameters of interest are estimated. A simulation study is performed to compare the methods and evaluate the impact of overdispersion.

Bayes Theorem↗
PubMed2001

Increased sensitivity to thyroid hormone in mice with complete deficiency of thyroid hormone receptor alpha.

Only three of the four thyroid hormone receptor (TR) isoforms, alpha1, beta1, and beta2, bind thyroid hormone (TH) and are considered to be true TRs. TRalpha2 binds to TH response elements on DNA, but its role in vivo is still unknown. We produced mice completely deficient in TRalpha (TRalpha(o/o)) that maintain normal serum thyroid-stimulating hormone (TSH) concentration despite low serum thyroxine (T(4)), suggesting increased sensitivity to TH. We therefore examined the effects of TH (L-3,3',5-triiodothyronine, L-T3) given to TH-deprived and to intact TRalpha(o/o) mice. Controls were wild-type (WT) mice of the same strain and mice resistant to TH due to deficiency in TRbeta (TRbeta(-/-)). In liver, T3 produced significantly greater responses in TRalpha(o/o) and smaller responses in TRbeta(-/-) as compared with WT mice. In contrast, cardiac responses to L-T3 were absent or reduced in TRalpha(o/o), whereas they were similar in WT and TRbeta(-/-) mice, supporting the notion that TRalpha1 is the dominant TH-dependent TR isoform in heart. 5-Triiodothyronine (L-T3) given to intact mice produced a greater suppression of serum T(4) in TRalpha(o/o) than it did in WT mice and reduced by a greater amount the TSH response to TSH-releasing hormone. This is an in vivo demonstration that a TR deficiency can enhance sensitivity to TH. This effect is likely due to the abrogation of the constitutive "silencing" effect of TRalpha2 in tissues expressing the TRbeta isoforms.

Animals↗
PubMed2001

In vitro trial of the pilot prototype of the prostate mechanical imaging system.

OBJECTIVES: To compare the sensitivity and accuracy of the mechanical imaging system (MI system) to that of the simulated digital rectal examination (DRE) in detecting nodules within fabricated rubber prostate phantoms. Mechanical imaging is a new technology for visualizing and characterizing tissues using mechanical strain and stress data. METHODS: Twelve rubber phantoms were designed to simulate human prostates. Ten phantoms contained hard nodules in various locations. Two phantoms contained no nodules. Each model was examined with the MI system by a urologist (R.E.W.) and research student. Three-dimensional images of the examined prostate phantoms with and without nodules were generated by the MI system software. Blind DRE was performed on each phantom independently by the urologist and student. The results of the MI examinations and DREs were compared for sensitivity in detecting the presence and location of nodules within the prostate phantoms. RESULTS: Three-dimensional MI images reconstructed from both the student and the urologist examination data demonstrated 100% of the nodules in the appropriate locations. The DREs by the urologist detected 83% of the nodules in the appropriate locations. The DREs by the student detected 67% of the nodules in the appropriate locations. CONCLUSIONS: The prostate MI system allowed the detection of nodules in the prostate phantoms with sensitivity exceeding that of an experienced urologist. In contrast to the DRE, the results of the MI examination appear to be independent of the operator's experience. Therefore, the MI system is a promising means of accurate, sensitive, objective, and recordable detection of hard nodules within the prostate.

Diagnosis, Computer-Assisted↗
PubMed2001

Congenital hypothyroidism in a child with unsuspected familial dysalbuminemic hyperthyroxinemia caused by a mutation (R218H) in the human albumin gene.

We found familial dysalbuminemic hyperthyroxinemia (FDH) in a 5-month-old boy with congenital hypothyroidism (CH) who had a blood thyrotropin (TSH) level of 479 mU/L but normal total serum thyroxine (T4) and higher than normal total triiodothyronine (T3) levels. Thyroid hormone substitution began at 5 weeks of age when T4 and T3 concentrations were below normal. Until the age of 5 months, treatment with levothyroxine was suboptimal on the basis of high serum TSH levels despite above-normal T4 levels. FDH was confirmed by isoelectric focusing and testing of other family members. DNA analysis of the patient revealed R218H, a mutation in the serum albumin gene associated with FDH, which was also present in the patient's euthyroid father and brother. Thyroid scans, serum thyroglobulin measurements, and free T4 measurements using equilibrium dialysis or 2-step immunoassay methods can identify thyroid hormone-binding protein defects and simplify the diagnosis and treatment of infants with CH.

Albumins↗
PubMed2001

Bayesian selection of continuous-time Markov chain evolutionary models.

We develop a reversible jump Markov chain Monte Carlo approach to estimating the posterior distribution of phylogenies based on aligned DNA/RNA sequences under several hierarchical evolutionary models. Using a proper, yet nontruncated and uninformative prior, we demonstrate the advantages of the Bayesian approach to hypothesis testing and estimation in phylogenetics by comparing different models for the infinitesimal rates of change among nucleotides, for the number of rate classes, and for the relationships among branch lengths. We compare the relative probabilities of these models and the appropriateness of a molecular clock using Bayes factors. Our most general model, first proposed by Tamura and Nei, parameterizes the infinitesimal change probabilities among nucleotides (A, G, C, T/U) into six parameters, consisting of three parameters for the nucleotide stationary distribution, two rate parameters for nucleotide transitions, and another parameter for nucleotide transversions. Nested models include the Hasegawa, Kishino, and Yano model with equal transition rates and the Kimura model with a uniform stationary distribution and equal transition rates. To illustrate our methods, we examine simulated data, 16S rRNA sequences from 15 contemporary eubacteria, halobacteria, eocytes, and eukaryotes, 9 primates, and the entire HIV genome of 11 isolates. We find that the Kimura model is too restrictive, that the Hasegawa, Kishino, and Yano model can be rejected for some data sets, that there is evidence for more than one rate class and a molecular clock among similar taxa, and that a molecular clock can be rejected for more distantly related taxa.

Animals↗
PubMed2001

Genetic analysis reveals different functions for the products of the thyroid hormone receptor alpha locus.

Thyroid hormone receptors are encoded by the TRalpha (NR1A1) and TRbeta (NR1A2) loci. These genes are transcribed into multiple variants whose functions are unclear. Analysis by gene inactivation in mice has provided new insights into the functional complexity of these products. Different strategies designed to modify the TRalpha locus have led to strikingly different phenotypes. In order to analyze the molecular basis for these alterations, we generated mice devoid of all known isoforms produced from the TRalpha locus (TRalpha(0/0)). These mice are viable and exhibit reduced linear growth, bone maturation delay, moderate hypothermia, and reduced thickness of the intestinal mucosa. Compounding TRalpha(0) and TRbeta(-) mutations produces viable TRalpha(0/0)beta(-/-) mice, which display a more severe linear growth reduction and a more profound hypothermia as well as impaired hearing. A striking phenotypic difference is observed between TRalpha(0/0) and the previously described TRalpha(-/-) mice, which retain truncated TRDeltaalpha isoforms arising from a newly described promoter in intron 7. The lethality and severe impairment of the intestinal maturation in TRalpha(-/-) mice are rescued in TRalpha(0/0) animals. We demonstrate that the TRDeltaalpha protein isoforms, which are natural products of the TRalpha locus, are the key determinants of these phenotypical differences. These data reveal the functional importance of the non-T3-binding variants encoded by the TRalpha locus in vertebrate postnatal development and homeostasis.

Animals↗
PubMed2001

Resistance to thyroid hormone does not abrogate the transient thyrotoxicosis associated with gestation: report of a case.

We report the occurrence of transient thyrotoxicosis during pregnancy in a subject with resistance to thyroid hormone. Before pregnancy, the subject was euthyroid, with normal serum TSH and elevated levels of free T(3) and free T(4) caused by a mutation in the TRbeta gene (R243Q). Beginning at the fourth week of gestation serum levels of free T(3) and T(4) increased in parallel with an increase in hCG. At 6-7 wk gestation she manifested hypermetabolic features, with mild nausea and vomiting. Peak levels of serum hCG and thyroid hormone concentrations were attained at 12 wk gestation, when serum TSH was fully suppressed. In the following weeks of gestation, thyroid hormone levels declined, with amelioration of the symptoms. A baby boy also affected with resistance to thyroid hormone harboring the same TRbeta gene mutation was born by normal vaginal delivery.

Adult↗
PubMed2001

State-of-the-art prostate cancer treatment and research. A report from the Cancer Institute of New Jersey.

Prostate cancer is a devastating disease that will be diagnosed in approximately 200,000 men in 2001. New methods for screening, prevention, and treatment are being developed. In addition, novel agents for the treatment of resistant prostate cancer are being developed in clinical trials. This review summarizes the recent efforts in diet, screening, novel systemic therapies, and alternative medicine for prostate cancer.

Adult↗
PubMed2001

Medical mimics. Medical and neurological conditions simulating ADHD.

The medical and neurological conditions that simulate ADHD are reviewed, as well as those disorders frequently presenting as comorbidities with ADHD. The localization of ADHD has invoked multiple areas, including frontal lobes, nondominant parietal lobe, and basal ganglia, and the neural network theory of cortical-subcortical-cortical loops has been implicated in the pathogenesis of ADHD. The medical evaluation of patients presenting with ADHD should be comprehensive, with an emphasis on demonstrating chronic and permeating symptoms since early childhood without a better medical explanation. Associated thyroid disorders are reviewed, including the syndrome of resistance to thyroid hormone. Suggested laboratory studies are provided, depending on the clinical circumstances.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Ureteroenteric anastomosis in continent urinary diversion: long-term results and complications of direct versus nonrefluxing techniques.

PURPOSE: Controversy exists over the importance of antireflux mechanisms in large volume, low pressure intestinal bladder substitutions. Despite the theoretical benefits of reflux prevention, antirefluxing ureteral reimplantations may have a greater risk of anastomotic stricture. We hypothesize that this inherent stricture rate may outweigh the potential benefits associated with reflux prevention. To assess this question critically we compare our results to those of direct and nonrefluxing techniques of ureterointestinal anastomosis during continent diversion. MATERIALS AND METHODS: Between 1990 and 1998, 58 patients underwent continent urinary diversion using an Indiana pouch or ileal orthotopic neobladder following cystectomy for muscle invasive bladder cancer. A total of 56 renal units were implanted using an end-to-side Nesbit direct anastomosis and 60 were implanted in a nonrefluxing manner. Clinical end points included anastomotic stricture formation, hydronephrosis, pyelonephritis, upper tract stone formation and renal deterioration, and were assessed with a mean followup of 41 months. RESULTS: Of 60 nonrefluxing ureteroenteric anastomoses 8 (13%) resulted in nonneoplastic stricture formation compared to 1 of 56 (1.7%) direct anastomoses, which was statistically significant (Fisher's exact test p <0.05). Strictures occurred up to 6 years following the original surgery. There was no significant difference between the 2 groups in regard to hydronephrosis, pyelonephritis, upper tract stone formation or azotemia. CONCLUSIONS: Nonrefluxing methods of ureterointestinal reimplantation resulted in a statistically significant higher rate of anastomotic stricture than the end-to-side direct anastomosis. This finding appears to outweigh any theoretical benefits of preventing pyelonephritis, stones or azotemia. For patients undergoing large volume, low pressure continent diversion the refluxing ureterointestinal anastomosis may be the technique of choice since it preserves renal function as well as the nonrefluxing method, is technically easier to perform and poses less risk of stricture. Delayed stricture formation years after surgery underscores the necessity for long-term radiological followup in patients following continent diversion.

Adult↗
PubMed2000

Lymphatic mapping and intraoperative lymphoscintigraphy for identifying the sentinel node in penile tumors.

Lymph node mapping has become an integral part of the management of melanoma and breast cancer with regard to both staging and treatment. We report our technique for lymphatic mapping and intraoperative lymphoscintigraphy applied to a patient with penile melanoma. This technique may improve the sensitivity of identifying the sentinel lymph node in patients with malignant penile lesions.

Aged↗