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Biomedical subjects

R E Goldstein

Publications and source records attributed to R E Goldstein.

At least 19 recordsLinked to original sources

Minimally invasive radioguided parathyroidectomy (MIRP).

The technique of parathyroidectomy has traditionally involved a bilateral exploration of the neck with the intent of visualizing 4 parathyroid glands and resecting pathologically enlarged glands. Parathyroid scanning using technetium-99m sestamibi has evolved and can now localize 80% to 90% of parathyroid adenomas. The technique of minimally invasive radioguided parathyroidectomy (MIRP) is a surgical option for most patients with primary hyperparathyroidism and a positive preoperative parathyroid scan. The technique makes use of a hand-held gamma probe that is used intraoperatively to guide the dissection in a highly directed manner with the procedure often performed under local anesthesia. The technique results in excellent cure rates while allowing most patients to leave the hospital within a few hours after the completion of the procedure. Current data also suggest the procedure can decrease hospital charges by approximately 50%. This technique may significantly change the management of primary hyperparathyroidism.

Equipment Design↗

Resetting wave forms in dictyostelium territories.

The mechanism by which spiral wave patterns appear in populations of Dictyostelium was probed experimentally by external chemical perturbation. Spiral waves, which often arise from the breakup of circular waves driven by pacemakers, typically entrain those pacemakers. We studied these processes by resetting the waves with a spatially uniform pulse of extrinsic cyclic AMP. A pattern of spirals reappeared if resetting was early in the signaling stage, but only targets emerged following late resetting, in a manner analogous to cardiac defibrillation. This supports recent hypotheses that wave pattern selection naturally occurs by slow temporal variation of the excitability of the cells.

Animals↗

Use of percutaneous ethanol injection for treatment of bilateral hyperplastic thyroid nodules in cats.

OBJECTIVE: To determine the efficacy and safety of percutaneous ethanol injection (PEI) for the treatment of hyperthyroidism caused by bilateral hyperplastic thyroid nodules in cats. DESIGN; Prospective study. ANIMALS: 7 cats. PROCEDURE: Hyperthyroidism was diagnosed on the basis of clinical signs and increased serum total thyroxine (TT4) concentrations. The presence of 2 cervical thyroid nodules was confirmed by use of ultrasonography and technetium Tc 99m albumin thyroid scans. After the death of 1 cat that received PEI in both thyroid nodules at the same time, the protocol was changed to injecting ethanol into 1 nodule at a time, with at least 1 month between injections. Clinical signs, serum TT4 concentrations, serum ionized calcium concentrations, laryngeal function, findings on ultrasonographic examinations of the ventral cervical region, and results of thyroid scans were monitored. RESULTS: Serum TT4 concentrations transiently decreased in all 6 cats (into the reference range in 5 of 6 cats) within 4 days of the first staged ethanol injection. Each subsequent injection resulted in a transient decrease in serum TT4 concentration. The longest period of euthyroidism was 27 weeks. Adverse effects included Horner's syndrome, dysphonia, and laryngeal paralysis. One cat died of unrelated causes. One cat underwent bilateral thyroidectomy, 2 cats were treated with methimazole, and 2 cats that had increased serum TT4 concentrations were not treated further, because they remained clinically normal. CONCLUSIONS AND CLINICAL RELEVANCE: Percutaneous ethanol ablation of bilateral thyroid nodules as a treatment for cats with hyperthyroidism is not recommended. This treatment is not as efficacious as the medical and surgical treatments presently used.

Administration, Cutaneous↗

Groucho augments the repression of multiple Even skipped target genes in establishing parasegment boundaries.

Groucho acts as a co-repressor for several Drosophila DNA binding transcriptional repressors. Several of these proteins have been found to contain both Groucho-dependent and -independent repression domains, but the extent to which this distinction has functional consequences for the regulation of different target genes is not known. The product of the pair-rule gene even skipped has previously been shown to contain a Groucho-independent repression activity. In the Even skipped protein, outside the Groucho-independent repression domain, we have identified a conserved C-terminal motif (LFKPY), similar to motifs that mediate Groucho interaction in Hairy, Runt and Hückebein. Even skipped interacts with Groucho in yeast and in vitro, and groucho and even skipped genetically interact in vivo. Even skipped with a mutated Groucho interaction motif, which abolished binding to Groucho, showed a significantly reduced ability to rescue the even skipped null phenotype when driven by the complete even skipped regulatory region. Replacing this motif with a heterologous Groucho interaction motif restored the rescuing function of Even skipped in segmentation. Further functional assays demonstrated that the Even skipped C terminus acts as a Groucho-dependent repression domain in early Drosophila embryos. This novel repression domain was active on two target genes that are normally repressed by Even skipped at different concentrations, paired and sloppy paired. When the Groucho interaction motif is mutated, repression of each target gene is reduced to a similar extent, with some activity remaining. Thus, the ability of Even skipped to repress different target genes at different concentrations does not appear to involve differential recruitment or function of Groucho. The accumulation of multiple domains of similar function within a single protein may be a common evolutionary mechanism that fine-tunes the level of activity for different regulatory functions.

Amino Acid Motifs↗

Intraoral camera helps predict and prevent tooth loss.

The video exam has proven to be a most effective means of re-establishing trust between patient and dentist by making the patient a co-diagnostician. In fact, it is not uncommon for patients to stop the diagnosis and ask specific questions about what they see. They can begin to diagnose pathology even before the dentist mentions it. A major benefit to the dentist is that invariably the exam reveals conditions not seen with typical clinical exams even using magnification loops. Although the intraoral camera has been around for more than a decade, its benefit during the video exam is more important now than ever before (8, 9). Every new patient and all patients of record should have the benefit of a video exam, as well as the dentist.

Dental Caries↗

Twirling and whirling: viscous dynamics of rotating elastic filaments.

Motivated by diverse phenomena in cellular biophysics, including bacterial flagellar motion and DNA transcription and replication, we study the overdamped nonlinear dynamics of a rotationally forced filament with twist and bend elasticity. Competition between twist injection, twist diffusion, and writhing instabilities is described by coupled PDEs for twist and bend evolution. Analytical and numerical methods elucidate the twist/bend coupling and reveal two regimes separated by a Hopf bifurcation: (i) diffusion-dominated axial rotation, or twirling, and (ii) steady-state crankshafting motion, or whirling. The consequences of these phenomena for self-propulsion are investigated, and experimental tests proposed.

Bacterial Physiological Phenomena↗

Chiral self-propulsion of growing bacterial macrofibers on a solid surface.

Supercoiling motions that accompany the growth of bacterial macrofibers (multicellular filamentous structures formed in B. subtilis by cell division without separation) are responsible for rolling, pivoting, and walking of fibers on a surface. Fibers possess a fulcrum about which they pivot and step in a chiral manner; forces and torques associated with cell growth, when blocked by friction, result in self-propulsion. The elastic engine that drives macrofiber motions generates torques estimated as microdyn cm and femtowatts of power; optical trapping studies yield a first direct measurement of the Young's modulus of the bacterial cell wall, the engine's "working fluid," of ca. 0.05 GPa.

Bacillus subtilis↗

Bistable helices.

We extend elasticity theory of filaments to encompass systems, such as bacterial flagella, that display competition between two helical structures of opposite chirality. A general, fully intrinsic formulation of the dynamics of bend and twist degrees of freedom is developed using the natural frame of space curves, spanning from the inviscid limit to the viscously overdamped regime applicable to cellular biology. Aspects of front propagation found in flagella are discussed.

Bacillus subtilis↗

Phospholipase C and termination of G-protein-mediated signalling in vivo.

In Drosophila photoreceptors, phospholipase C (PLC) and other signalling components form multiprotein structures through the PDZ scaffold protein INAD. Association between PLC and INAD is important for termination of responses to light; the underlying mechanism is, however, unclear. Here we report that the maintenance of large amounts of PLC in the signalling membranes by association with INAD facilitates response termination, and show that PLC functions as a GTPase-activating protein (GAP). The inactivation of the G protein by its target, the PLC, is crucial for reliable production of single-photon responses and for the high temporal and intensity resolution of the response to light.

Animals↗

Effect of minimally invasive radioguided parathyroidectomy on efficacy, length of stay, and costs in the management of primary hyperparathyroidism.

OBJECTIVE: To compare the first 20 patients who underwent minimally invasive radioguided parathyroidectomies (MIRPs) performed at the authors' institution with 20 similar patients who underwent a more conventional surgical approach for primary hyperparathyroidism. SUMMARY BACKGROUND DATA: The technique of parathyroidectomy has traditionally involved a bilateral exploration of the neck with the intent of visualizing four parathyroid glands and resecting enlarged parathyroid glands. Parathyroid scanning using radioisotopes has evolved and now can localize adenomas in 80% to 90% of patients. MIRP combines parathyroid scanning with a hand-held intraoperative detector that guides the surgeon to the adenoma. METHODS: Forty patients with documented primary hyperparathyroidism who underwent surgery by a single surgeon between January 1998 and May 1999 were included in this study. Twenty of these patients underwent MIRP. The technique involved injecting 20 mCi technetium-99m sestamibi 2 hours before surgery and performing a parathyroid scan. If the scan was considered positive for a single adenoma, patients were taken to the operating room and given the choice of either general anesthesia or intravenous sedation with local anesthesia. Using an incision of 4 cm or less, the dissection down to the adenoma was guided by the Navigator miniature hand-held probe. An additional 20 patients who underwent more conventional bilateral or unilateral neck exploration were chosen to match the MIRP patient population. Both groups included four patients undergoing repeat surgery for persistent or recurrent primary hyperparathyroidism and one patient with multiple endocrine neoplasia type 1 syndrome. Patient demographics, preoperative calcium and parathyroid hormone levels, operative time, total time in the operating room, time in the recovery room, complications, hospital charges for the operating room, and total hospital charges were analyzed. RESULTS: There were no differences in patient demographics, presenting symptoms, or preoperative calcium level between patients undergoing the standard procedure versus MIRP. Operative time, total time in the operating room, operative charges, and total hospital charges were significantly reduced in the MIRP group. All 40 patients were cured of primary hyperparathyroidism. There were no recurrent laryngeal nerve injures in either group. The mean length of stay in the standard group was 1. 35 days; in the MIRP group, 65% of patients were discharged within 5 hours after surgery. CONCLUSIONS: The MIRP technique resulted in excellent cure rates for primary hyperparathyroidism while simultaneously decreasing operative time and hospital stays. These resulted in significant cost reductions without compromising patient safety. The technique may significantly change the management of primary hyperparathyroidism.

Adenoma↗

Computer imaging versus conventional esthetic consultation: a prospective clinical study.

Computer imaging can be helpful in demonstrating to patients the potential outcome of esthetic dental procedures. The current clinical study assesses the effectiveness of computer imaging by comparing the reactions of patient and dentist to conventional consultations versus the use of computer imaging. The responses from 35 subjects show that computer imaging consultations are more effective in helping patients decide to accept treatment. Patient satisfaction was higher (93.75%) with computer consultations than with conventional methods (83.3%). Computer imaging consultations were easier to conduct but significantly (p < .05) more time consuming.

Adult↗

Twenty-five-year surgical experience with pheochromocytoma in children.

Our objective was to analyze the presentation, diagnostic localization, operative management, histology, and long-term outcome of a single center's experience with pheochromocytomas in children. A chart review was done to identify all operatively managed pheochromocytomas in patients age 18 years or younger. Open and laparoscopic cases were included. We reviewed the presentation, diagnostic imaging, localization, operative management, pathology, and postoperative outcome of these patients. Clinic visits, contact with the tumor registry, and telephone interviews were used for follow-up. From 1973 through 1999, there were 11 children (four males and seven females) with 14 pheochromocytomas. Two (18.2%) patients had bilateral adrenal lesions and one patient had both adrenal and extra-adrenal tumors. Six (54.5%) patients had extra-adrenal lesions. The average age at operation was 14.7 years (range 9-18 years). Nine (82%) patients had significant hypertension at presentation. CT was used to localize the tumor in eight patients and urine catecholamine levels were used to confirm the diagnosis. Two of the cases were associated with inherited syndromes (multiple endocrine neoplasia 2A and von Hippel-Lindau). Ten patients underwent an open operation and one patient had a laparoscopic resection. The average patient follow-up was 9.2 years (range 9 months to 25 years). There were no operative complications and all patients were alive and well at the time of last follow-up. Three patients (27.2%) had tumors with microscopic malignant features. No tumors recurred or had evidence for metastatic spread. We conclude that peak incidence of pheochromocytomas in children is in early adolescence. Resection can be carried out safely with minimal morbidity and mortality. Current best management of this entity includes establishment of a biochemical diagnosis, adequate preoperative blockade, appropriate imaging, and an individualized operative approach based on tumor location and size.

Adolescent↗

Percutaneous ultrasound-guided chemical parathyroid ablation for treatment of primary hyperparathyroidism in dogs.

OBJECTIVE: To evaluate the efficacy, feasibility, and safety of ultrasound-guided chemical ablation of parathyroid masses in dogs with primary hyperparathyroidism. DESIGN: Prospective clinical trial. ANIMALS: 8 dogs. PROCEDURE: In all dogs, a solitary parathyroid mass was evident ultrasonographically. Dogs were anesthetized with propofol, and a 27-gauge needle was directed into the parathyroid mass under ultrasound guidance. Ethanol (96%) was injected into the mass until there was evidence of diffusion of fluid throughout the mass. Serum total calcium, ionized calcium, phosphorus, and parathyroid hormone (PTH) concentrations were monitored daily for 5 to 7 days after the ablation procedure and again 1, 3, and 6 months after the procedure. Dogs were also monitored for adverse effects. Follow-up ultrasonography was performed 5 days and 1 month after the ablation procedure. RESULTS: One injection was required in 7 dogs, and 2 injections were required in 1. Serum total and ionized calcium concentrations were within reference ranges within 24 hours after treatment in 7 dogs and within 5 days in 1 dog. Serum PTH concentration decreased and serum phosphorus concentration increased within 24 hours after treatment in all 8 dogs. Transient hypocalcemia developed in 4 dogs during the first 5 days after treatment, but only 1 dog required treatment for hypocalcemic tetany. Hypercalcemia recurred in 1 dog 1 month after the procedure and surgical removal of the parathyroid mass was required. Other adverse effects were not reported. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasound-guided chemical ablation of parathyroid masses is a safe and effective alternative to surgery for dogs with primary hyperparathyroidism.

Adenoma↗

Thrombogenic factors and recurrent coronary events.

BACKGROUND: Thrombosis is a pivotal event in the pathogenesis of coronary disease. We hypothesized that the presence of blood factors that reflect enhanced thrombogenic activity would be associated with an increased risk of recurrent coronary events during long-term follow-up of patients who have recovered from myocardial infarction. METHODS AND RESULTS: We prospectively enrolled 1045 patients 2 months after an index myocardial infarction. Baseline thrombogenic blood tests included 6 hemostatic variables (D-dimer, fibrinogen, factor VII, factor VIIa, von Willebrand factor, and plasminogen activator inhibitor-1), 7 lipid factors [cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, lipoprotein(a), apolipoprotein (apo)A-I, and apoB], and insulin. Patients were followed up for an average of 26 months, with the primary end point being coronary death or nonfatal myocardial infarction, whichever occurred first. The hemostatic, lipid, and insulin parameters were dichotomized into their top and the lower 3 risk quartiles and evaluated for entry into a Cox survivorship model. High levels of D-dimer (hazard ratio, 2.43; 95% CI, 1.49, 3.97) and apoB (hazard ratio, 1.82; 95% CI, 1.10, 3.00) and low levels of apoA-I (hazard ratio, 1.84; 95% CI, 1.10, 3.08) were independently associated with recurrent coronary events in the Cox model after adjustment for 6 relevant clinical covariates. CONCLUSIONS: Our findings indicate that a procoagulant state, as reflected in elevated levels of D-dimer, and disordered lipid transport, as indicated by low apoA-1 and high apoB levels, contribute independently to recurrent coronary events in postinfarction patients.

Adult↗

Laparoscopic left adrenalectomy for pheochromocytoma in a child.

Although uncommon, adrenalectomy occasionally is indicated in children. To date, this procedure has required either a laparotomy or a flank incision. The authors report the case of a child with episodic palpitations, diaphoresis, chest discomfort, and occipital headache who underwent laparoscopic adrenalectomy for pheochromocytoma without complication.

Adrenal Gland Neoplasms↗

Insulin- and glucagon-independent effects of calcitonin gene-related peptide in the conscious dog.

Calcitonin gene-related peptide (CGRP) causes vasodilation in many vascular beds, resulting in hypotension and tachycardia. The current studies were conducted in overnight-fasted conscious dogs to determine the effect of different CGRP dosages on carbohydrate metabolism and catecholamine release resulting from hemodynamic changes. During a pancreatic clamp, dogs received intraportal infusions of CGRP at 13, 26, and 52 (n = 3) or 52, 105, and 210 pmol x kg(-1) x min(-1) (n = 4; 60 minutes at each rate). Blood pressure decreased (P < .05) and the heart rate and hepatic blood flow (HBF) increased a maximum of 100% and 30%, respectively (P < .05). For the five CGRP infusion rates, arterial plasma epinephrine increased approximately 1.3-, 2.4-, 7.4-, 12-fold, and eightfold basal, respectively; norepinephrine increased about 2.3-, 3.3-, 4.1-, 4.6-, and 4.8-fold basal, respectively; and cortisol increased about twofold, 3.4-fold, fivefold, sixfold, and 6.2-fold basal, respectively. At CGRP infusion rates of 52 pmol x kg(-1) x min(-1) or higher, increases (P < .05) occurred for plasma glucose, endogenous glucose production (EndoRa), and net hepatic uptake of gluconeogenic substrates (maximum change, 24 mg/dL, 1.3 mg x kg(-1) x min(-1), and 9.9 micromol x kg(-1) x min(-1), respectively). Arterial blood glycerol concentrations increased only a maximum of 30%. At the two highest CGRP infusion rates, glycerol returned to basal concentrations and arterial plasma nonesterified fatty acids (NEFAs) decreased. The increased net hepatic uptake of gluconeogenic substrates during CGRP infusion was sufficient to account for 49% to 58% of the increase in EndoRa. CGRP has no apparent direct effects on hepatic carbohydrate metabolism, but the catecholamines, at levels similar to those observed during CGRP infusion, stimulate hepatic glycogenolysis. Therefore, some factor(s) other than CGRP, probably an increase in circulating catecholamine concentrations, would appear to be responsible for at least 42% to 51% of the increase in EndoRa.

Alanine↗