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Biomedical subjects

D Zimmerman

Publications and source records attributed to D Zimmerman.

At least 37 records · Page 2Linked to original sources

Immunization with a LEAPS heteroconjugate containing a CTL epitope and a peptide from beta-2-microglobulin elicits a protective and DTH response to herpes simplex virus type 1.

A ligand epitope antigen presentation system (LEAPS) heteroconjugate vaccine containing a CTL epitope (H1) from the HSV-1 immediate early protein ICP27 (322-332) and a peptide sequence (J) from beta-2-microglobulin (35-50) elicited protection from intraperitoneal viral challenge and promoted DTH responses. The H1 peptide and other H1 containing heteroconjugates did not elicit protection or DTH responses. Antibody to the H1 peptide could not be detected by ELISA following vaccination with peptide, heteroconjugate or natural infection. The LEAPS heteroconjugate appears to prime a Thl-like response which is subsequently boosted by infection. These studies show that attachment of the J peptide can make a CTL epitope into a vaccine which is immunogenic and promotes a protective Th1 type of response.

Amino Acid Sequence↗

Adrenal suppression secondary to inhaled fluticasone propionate.

BACKGROUND: Inhaled glucocorticoids are the medical treatment of choice in many of patients with asthma. Fluticasone propionate is an inhaled glucocorticoid with little systemic bioavailability via the oral route and infrequent association with systemic adverse effects at the recommended dosage. OBJECTIVE: To report a case of adrenal suppression and exogenous glucocorticoid excess from inhaled fluticasone propionate. METHODS: A 9-year-old girl with a previous history of episodic asthma was placed on 550 microg of fluticasone propionate daily for severe labile asthma diagnosed by history and methacholine challenge. The patient returned 6 months later with complaints of increased appetite, nausea, and feeling "hot and flushed." On physical exam she had stigmata of Cushing's syndrome. The patient subsequently developed orthostatic hypotension and moderate dehydration following a viral illness. After a long taper of fluticasone propionate the patient' s adrenal function returned to normal and she had no acute or chronic exacerbations of her asthma. RESULTS: Her 8 AM cortisol was undetectable with an ACTH of 21 pg/mL. The serum prolactin, TSH, free thyroxine, insulin-like growth factor I, and renin activity were all normal. An MRI study of her head was also normal. Repeat methacholine challenges while receiving a much smaller dose fluticasone propionate showed a significant decrease in airway reactivity. CONCLUSION: Adrenal suppression can occur from inhaled fluticasone propionate at a dosage less than has been previously reported.

Administration, Inhalation↗

Fetal and neonatal hyperthyroidism.

Fetal and neonatal hyperthyroidism are usually produced by transplacental passage of thyroid-stimulating immunoglobulins. Most commonly, the thyroid-stimulating immunoglobulins are a component of active maternal Graves' disease. However, such antibodies may continue to be produced after ablation of the thyroid by surgery, radioiodine, or by the immune mechanisms of Hashimoto's thyroiditis. Other mechanisms that have produced fetal and neonatal hyperthyroidism include activating mutations of the stimulatory G protein in McCune-Albright syndrome and activating mutations of the thyrotropin (TSH) receptor. Fetal hyperthyroidism may be associated with intrauterine growth retardation, nonimmune fetal hydrops, craniosynostosis, and intrauterine death. Features of this condition in the neonate include hyperkinesis, diarrhea, poor weight gain, vomiting, ophthalmopathy, cardiac failure and arrhythmias, systemic and pulmonary hypertension, hepatosplenomegaly, jaundice, hyperviscosity syndrome, thrombocytopenia, and craniosynostosis. The time course of thyrotoxicosis depends on etiology. Remission by 20 weeks is most common in neonatal Graves' disease; remission by 48 weeks is nearly always seen. A subset of these patients may have persistent disease when there is a strong family history of Graves' diseases. Disease persistence is characteristic of patients with activating mutations of the TSH receptor. Treatment of fetal hyperthyroidism comprises administration of antithyroid drugs to the mother. Fetal heart rate and fetal growth should be monitored. Ultrasonography may reveal changes in thyroid size. At times, cordocentesis may be useful for monitoring fetal thyroid function. Hyperthyroid neonates may be treated with antithyroid drugs, beta-adrenergic receptor blocking agents, iodine, or iodinated contrast agents, and at times, with glucocorticoids and digoxin. Nonremitting causes of neonatal hyperthyroidism require ablative treatments such as thyroidectomy.

Female↗

Continuous veno-venous haemodialysis with a novel bicarbonate dialysis solution: prospective cross-over comparison with a lactate buffered solution.

OBJECTIVE: To compare acid-base balance, lactate concentration and haemodynamic parameters during continuous veno-venous haemodialysis (CVVHD) using bicarbonate or a lactate buffered dialysate. METHODS DESIGN: prospective randomized cross-over design; SETTING: Multicentre combined adult surgical and medical intensive care units. Patients; 26 critically ill patients starting CVVHD for acute renal failure. INTERVENTIONS: Each patient to receive 48 h of bicarbonate dialysate and 48 h of lactate dialysate with the order of the 48 h block randomized at trial entry. RESULTS: The serum bicarbonate increased from baseline in both the lactate and bicarbonate groups over the first 48 h of treatment (16.3+/-1.53 to 22.2+/-1.41 mmol/l and 18.9+/-2.02 to 22.2+/-1.18 mmol/l, respectively) and continued to rise towards normal over the next 48 h after cross-over to the other dialysate. The H+ and pCO2 only trended higher in the lactate group. Unlike the acid base parameters, serum lactate levels varied depending on the dialysate composition. The patients initially randomized to the lactate dialysate had higher serum lactate levels and these tended to increase further after 48 h of dialysis from 2.4+/-0.8 to 2.6+/-0.4 mmol/l. However, in the following 48 h the lactate levels fell to 1.8+/-0.6 (P = 0.039) while patients were being treated with the bicarbonate dialysate. Similar results were seen in the patients initially randomized to the bicarbonate dialysate. Serum lactate remained stable over the first 48h (1.4+/-0.2 to 1.5+/-0.1 mmol/l) but after cross-over to the lactate dialysate increased to 3.1+/-0.7 mmol/l (P = 0.051). Overall, lactate levels were significantly higher during dialysis with lactate buffered solution than bicarbonate buffered solution (2.92+/-0.45 vs. 1.61+/-0.25 mmol/l P = 0.01). Mean arterial pressure trended higher during bicarbonate dialysis but did not reach statistical significance (lactate vs. bicarbonate; 71.1+/-3.1 vs. 81.3+/-5.8 mm Hg). Subgroup analysis of the patients with abnormal liver indices or increased lactate levels at initiation of dialysis (n = 15) revealed only a trend toward better bicarbonate control (lactate vs. bicarbonate; 22.00+/-1.73 vs. 22.86+/-1.09, P = 0.2). However, in this group with hepatic insufficiency elevations in serum lactate were even greater during lactate compared to the bicarbonate dialysis (3.39+/-0.68 vs. 1.78+/-0.42 P = 0.036). Patients who had elevations of lactate during lactate dialysis had a high mortality (6 of 7). These patients had an even greater disparity in lactate levels (4.3+/-1.4 vs. 1.3 +/-0.3) and blood pressure (68.0+/- 7.7 vs. 87.2+/-17.1) between lactate and bicarbonate dialysis. Due to small patient numbers these comparisons did not achieve statistical significance. CONCLUSION: During continuous veno venous haemodialysis a bicarbonate buffered dialysis solution provided equal acid-base control but maintained more normal lactate levels than a lactate buffered dialysis solution.

Acid-Base Equilibrium↗

Thyrotoxicosis in children.

Graves' disease is the predominant cause of hyperthyroidism in the pediatric age group. Other disorders must be recognized, however, because adequate management relies on a precise diagnosis. Careful monitoring of the thyroid status is required during this active phase of growth and development.

Adenoma↗

Bisphosphonates for treatment of childhood hypercalcemia.

Most clinicians only have a limited experience in treating childhood hypercalcemia with bisphosphonates. We report our experience in the use of intravenous and oral bisphosphonates in a 5-year-old with hypercalcemia secondary to acute lymphocytic leukemia, a 16-year-old with immobilization hypercalcemia, and a 14-year-old with chronic hypercalcemia of unknown cause. Single infusions of 0.5 mg/kg and 1 mg/kg of intravenous pamidronate were administered over 4 hours. No adverse reactions were observed except for hypocalcemia. A dose between 10 and 20 mg of oral alendronate was successfully used to maintain normocalcemia in the patient with chronic hypercalcemia. In our experience, the administration of bisphosphonates has enabled us to achieve normocalcemia in all cases, and in all cases there were no significant side effects. Long-term potential side effects from their use in children during the active phase of growth remain unknown.

Adolescent↗

Structural-functional bioinformatics: knowledge-based NMR interpretation.

This paper describes a knowledge-based approach to a problem of structural-functional bioinformatics, specifically the determination of protein structure through the automated analysis of NMR data. Highly successful results in carrying out sequence-specific assignments of residues from multidimensional NMR datasets has led us to automation of NOE dataset interpretation and a design for integrating these results with other protein structure and function analysis programs.

Computational Biology↗

Safety and clinical utility of long-term intravenous milrinone in advanced heart failure.

Few data are available on the long-term safety or clinical utility of the inodilator agent milrinone. We designed a prospective, nonrandomized, observational trial in a cohort of 71 patients who had demonstrated dependence on inotropic therapy, had been clinically stable on an inotropic regimen (milrinone, dobutamine, or both) for > or = 72 hours, and had been given intravenous milrinone for > 72 hours. Group I (n = 22) patients required treatment with both milrinone and dobutamine to achieve stability; group II (n = 49) patients attained stability initially with either milrinone (subgroup IIA) or dobutamine (subgroup IIB), but later required adjunctive therapy with the other inotropic agent for continued hemodynamic support. Of the 71 patients, 38% required mechanical intervention to achieve hemodynamic stability, and 68% were successfully bridged to heart transplantation. Patients were maintained on milrinone therapy for as long as 8 weeks and demonstrated a low incidence of adverse cardiac (7%) or noncardiac (4%) events. Subgroup IIA (28%) had significantly less need than subgroup IIB (52%) for mechanical intervention using an intraaortic balloon pump (p = 0.05), although mortality rates while awaiting transplantation were statistically similar in subgroups IIA (28%) and IIB (35%). Significant improvements from baseline values were noted at the time of transplantation for all aspects of systemic hemodynamics, indicating sustained long-term hemodynamic effects. Long-term intravenous milrinone therapy is safe and well tolerated, and it provides hemodynamic and metabolic support as a pharmacologic bridge to transplantation. The findings also suggest that milrinone as primary inodilator therapy may be associated with less need for mechanical ventricular support.

Adult↗

Insular thyroid carcinoma in adolescents: a potentially lethal endocrine malignancy.

BACKGROUND: Insular thyroid carcinoma is intermediate in aggressiveness between well differentiated and anaplastic thyroid carcinomas. METHODS: The authors describe two children with insular thyroid carcinoma who had markedly different outcomes. In the first case, a girl age 15 years, 2 months presented with a large pulsatile mass in the right thyroid lobe. In the second case, a girl age 16 years, 3 months presented after total thyroidectomy was performed elsewhere for confirmed pTNM Stage I insular thyroid carcinoma. RESULTS: In Case 1, total thyroidectomy was performed, and histologic examination revealed insular thyroid carcinoma with lymph node involvement. Six weeks postoperatively, neck masses reappeared. There was significant radioactive iodine uptake in the thyroid bed and in a palpable right supraclavicular lymph node; this was associated with an increased serum thyroglobulin level. Ultrasound-guided biopsy of the lymph node confirmed recurrent insular carcinoma, and neck dissection was performed. Six weeks later, there was 0.35% iodine uptake in the neck, and the patient was treated with 300 mCi of (131)I. She had no signs of recurrence when last seen 22 months postoperatively. In Case 2, the patient was given 29.9 mCi of (131)I for remnant ablation. Four months postoperatively, fine-needle aspiration biopsy of a high jugular lymph node demonstrated recurrence. The patient was given 200 mCi of (131)I but had no significant response. Right modified neck dissection was performed, followed by external beam radiation. Despite aggressive treatment with a further 500 mCi of (131)I, progressive lung and mediastinal metastases developed, followed by brain metastasis. The patient died 31 months after the initial diagnosis. CONCLUSIONS: Insular thyroid carcinoma may occur and behave aggressively in children. Vigorous initial surgical and radioactive iodine treatments are warranted.

Adolescent↗

Attained adult height after childhood asthma: effect of glucocorticoid therapy.

BACKGROUND: Although oral and inhaled glucocorticoid therapy may impair growth in children with asthma, the effect of glucocorticoid therapy and asthma on attained adult height has not been extensively studied in representative children in the community. OBJECTIVES: The study was designed to compare the attained adult height of children with asthma with the attained adult height of nonasthmatic children and to compare the attained adult height of asthmatic children treated with glucocorticoids with the attained adult height of asthmatic children who did not receive glucocorticoids. METHODS: Residents of Rochester, Minnesota, with onset of asthma from 1964 to 1987 and age- and sex-matched non-asthmatic residents of Rochester were studied. Glucocorticoid exposure was assessed from medical records. The mean of 5 stadiometer measurements of adult height, adjusted for sex and parental height, was analyzed. RESULTS: One hundred fifty-three patients with asthma (mean age at onset, 6.1 +/- 4.8 years) and 153 age- and sex-matched nonasthmatic subjects were studied. Adult height of patients with asthma (mean age at measurement, 25.7 +/- 5.2 years) was not significantly different from the adult height of non-asthmatic subjects; the overall difference, adjusted for mid-parental height, was -0.20 cm (95% confidence interval from -0.27 to 1.64). The adult height of asthmatic children treated with glucocorticoids was not significantly different from the adult height of patients with asthma not treated with glucocorticoids; the difference after adjusting for mid-parental height was -0.2 cm (95% confidence interval from -0.1 to 0.6). CONCLUSIONS: We conclude that the attained adult height of patients with asthma is not different from the adult height of age- and sex-matched nonasthmatic subjects and that the attained adult height of asthmatic children treated with glucocorticoids is not significantly different from the adult height of children not treated with glucocorticoids.

Administration, Inhalation↗

Using the Resident Assessment Instrument for quality enhancement in nursing homes.

BACKGROUND: in some current policy discussions concerning long-term care, the emphasis has been almost solely on the costs of care. This dialogue must be replaced with a discussion of value, which emphasizes both the costs of care and quality of care. While the Resident Assessment Instrument (RAI) was originally designed as a multidimensional assessment tool aimed at improving clinical practice, it can also provide the foundation for a comprehensive data base that can be used to assess and monitor the quality of care. AIMS and CONCLUSIONS: using data from four sites (in Denmark, Iceland, Italy and the USA) and eight indicators of quality that could be derived from single assessments, we demonstrate how quality might be measured and compared using the RAI. Although this is for illustrative purposes only it does show how this data base can provide invaluable information to providers about the quality of care within their facilities. It can also allow consumers and purchasers to evaluate the relative performance of different providers.

Aged↗

Thyroid neoplasia in children.

In 1995, the incidence of childhood thyroid cancer in England and Wales was only 0.5 cases per million children per year. Papillary cancers in younger children were histologically distinct from tumors in older individuals. The incidence of thyroid cancer in the vicinity of Chernobyl increased by 62 times within 5 years of the nuclear explosion. Mutations of the RET protooncogene (a growth factor receptor) occur in nearly all familial medullary thyroid carcinomas and may be used for family screening. RET is involved in chromosomal rearrangements in a majority of childhood papillary thyroid cancers. Fine-needle aspiration biopsy identifies the childhood thyroid nodules that are at greatest risk for cancer. It should be noted, however, that approximately 2% of aspirates are falsely negative. The adequacy of unilateral surgery for papillary thyroid cancers is controversial. Aggressive surgery for persistent medullary carcinoma produces remission in one third of patients. Novel radionuclide techniques are useful in detecting and treating metastatic medullary carcinoma.

Biopsy, Needle↗

Customer service: the new battlefield for market share.

In a survey conducted by the authors of the following article, it was determined that more than 50 percent of employers and managed care companies dropped providers who failed customer service standards. Many employers stated that they changed health plans according to their employees' preferences. Managed care organizations reported that they use the data from customer service surveys to choose providers, facilitate contract negotiations, and determine provider bonuses. Healthcare financial professionals can gain competitive advantages and help secure their organizations' financial future by focusing their resources and attention toward customer service issues.

Contract Services↗

Loss of the N-myc oncogene in a patient with a small interstitial deletion of the short arm of chromosome 2.

To our knowledge, only four previous cases of distal chromosome 2p deletions exist in the literature. We present a patient with minor facial anomalies who had a distal interstitial deletion of the short arm of chromosome 2, del(2)(p24.2p25.1). This patient had many features seen in other patients with distal 2p deletion including short stature, "rectangular" facies, microcephaly, hypotonia, and mental retardation. This patient also has sensorineural hearing loss which has been described in one other patient with a similar deletion. The N-myc oncogene has been mapped to 2p24. By fluorescence in situ hybridization using a cDNA probe for the N-myc oncogene, this patient was found to have a deletion of the N-myc oncogene. This confirms the previous map location for N-myc.

Abnormalities, Multiple↗

Concurrent hormone resistance (pseudohypoparathyroidism type Ia) and hormone independence (testotoxicosis) caused by a unique mutation in the G alpha s gene.

Defects in the G (guanine nucleotide-binding)-protein subunit (G alpha s) which stimulates adenylyl cyclase may result in either loss or gain of endocrine function. Reduced G alpha s activity is found in the hormone resistance syndrome, pseudohypoparathyroidism type Ia (PHP-Ia), while constitutive activation of G alpha s is associated with endocrine organ overactivity, including the gonadotropin-independent sexual precocity seen in patients with McCune-Albright syndrome. We identified two unrelated boys presenting with concurrent PHP-Ia and gonadotropin-independent sexual precocity (testotoxicosis). Mutational screening by denaturing gradient gel electrophoresis and sequencing of PCR-amplified exons of the G alpha s gene revealed a point mutation which generates an alanine-to-serine substitution in codon 366 of one G alpha s allele (A366S), an alanine present at the homologous position in all G-proteins. We have previously shown in transfected testis cells that the A366S mutation activates G alpha s by decreasing affinity for GDP, thereby increasing the rate of nucleotide exchange in a receptor-independent fashion. In contrast to differential stability of the activated mutant G alpha s protein in Leydig cells, with stability at 32 degrees C but not at 37 degrees C, skin fibroblasts with the mutation had the same reduced G alpha s levels at both temperatures. Our findings explain the limitation of clinical manifestations of G alpha s overactivity to testis, without involvement of other body appendages which are generally at lower than core body temperature. This unique mutation at a critically conserved residue of G alpha s is the first mutant G-protein which affects guanine nucleotide affinity and is associated with human disease, producing widely divergent and tissue-specific effects.

Blotting, Northern↗

Surgical treatment of Graves' disease in patients younger than 18 years.

Eighty-two children and adolescents (18 males, 64 females; median age 14 years) surgically treated for Graves' disease at a single institution between 1979 and 1993 were retrospectively reviewed. Most of the patients (74%) coming to thyroidectomy had been treated medically for a period ranging from 2 to 80 (median 15) months. Bilateral subtotal thyroid resection was the most frequently performed procedure (86%). Postoperatively, no permanent recurrent laryngeal nerve palsy or permanent hypocalcemia occurred. Operative mortality was zero. With a median follow-up of 8.3 years, recurrent hyperthyroidism occurred in five patients (6%), one of whom required reoperation. Most children and adolescents with Graves' disease can be rendered euthyroid by nonsurgical treatment options. However, prolonged and ineffective medical treatment should be avoided in these patients who are in the formative years of their lives. Surgical treatment, when indicated and employed, offers young patients with Graves' disease a safe, rapid, definitive, cost-effective treatment with a high success rate.

Adolescent↗

Applying performance measures to long-term care.

BACKGROUND: Nine nursing facilities in Mississippi participated in the American Health Care Association's Quality Indicator Index and Education (QUIIX-Ed) project to apply quantitative performance measurements to continuous quality improvement in long-term care. Begun in May 1994, with the first collection of performance measurement data in March 1995, the project used 15 measures of clinical care based on standardized assessments of resident conditions. METHODOLOGY: QUIIX-Ed assessed the impact of quality indicator information in nursing facilities based on Minimum Data Set resident assessments. Comparison reports allow each facility to profile its performance against that of other providers in the project. The project does not standardize the quality improvement process: the focus is on the incorporation of information into existing nursing care and quality improvement practices. OPERATIONAL ISSUES: Each month the facilities updated their quality indicator scores and exported those scores to a central database that aggregated scores to generate benchmarking statistics for each facility, including project medians, percentiles, and facility performance rankings. EXAMPLES: Two case studies on bedfast residents and restraint use illustrate the process of examining care issues identified by quality indicators, developing appropriate interventions, and evaluating the efficacy of the intervention. DISCUSSION: The limited intervention of introducing quantitative care measurements had a significant impact on resident outcomes and the nursing process. These measurements are readily incorporated into existing nursing practices and facility improvement efforts, regardless of the extent to which the quality improvement process has been developed.

Computer Communication Networks↗