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Biomedical subjects

S Weinstein

Publications and source records attributed to S Weinstein.

At least 37 records · Page 2Linked to original sources

Use of a low-prime circuit for bloodless heart transplantation in xenotransplant of 5-7 kilogram primates.

There is a great effort to decrease blood product use during open-heart surgery in pediatrics. We were presented with a research challenge to accomplish heart xenotransplantation from donor cynomologous monkey (Macaca fascicularis) to recipient olive baboon (Papio anubis) of 5-7 kilograms without benefit of donor or banked blood products. The purpose of this study was to design and implement a practical, low-volume circuit to minimize hemodilution and avoid the use of blood products. A simple circuit was assembled using a low-volume oxygenator with hardshell venous reservoir, an 1/8-inch arterial line, an 1/4-inch venous line, and gravity drainage. Three xenotransplants were performed and evaluated. The mean recipient weights were 6.3 +/- 0.7 kg. Circuit prime volume was 228 +/- 5.8 mL, and bypass time was 85 +/- 6.7 min. Blood flow rates were 585 +/- 113 mL/min with postmembrane arterial line pressures of 344 +/- 81 mmHg, and patient mean arterial pressures (MAP) of 51.4 +/- 16.7 mmHg. Venous saturations were 63.7 +/- 8.0%. The hematocrit prebypass was 37.4 +/- 3.2, bypass 20.7 +/- 0.9, post-MUF 27.8 +/- 3.3, and 7 days postoperative 24.5 +/- 7.5%. Platelet count was 289 +/- 1.1 K/microL, 147 +/- 37.1 K/microL, and 322 +/- 292.7 K/microL prebypass, postbypass, and 7 days postoperative, respectively. Plasma-free hemoglobin prebypass was 7.5 +/- 4.4 mg/dL and postbypass 22.2 +/- 16.5 mg/dL with no noted hematuria during and after the procedure. All patients survived and were successfully weaned from cardiopulmonary bypass (CPB) with same day extubation. A low-prime circuit for bloodless heart surgery is possible. To achieve low reservoir levels, especially without the use of an arterial line filter (ALF), it is necessary to have a full armament of monitoring and alarm devices.

Animals↗

Early survival of infants weighing 2.5 kilograms or less undergoing first-stage reconstruction for hypoplastic left heart syndrome.

BACKGROUND: Results of staged palliation for hypoplastic left heart syndrome (HLHS) have improved in recent years; however, certain risk factors have been associated with decreased survival rates. METHODS AND RESULTS: We retrospectively reviewed the medical records of 67 patients weighing </=2.5 kg undergoing the first stage of reconstructive surgery at our institution between January 1, 1990, and December 31, 1997. HLHS was present in 45 patients, complex double-outlet right ventricle in 10, unbalanced AV canal in 5, tricuspid atresia with transposition of the great vessels in 4, and other diagnoses in 3. Mean age at surgery was 10.1+/-10.7 days (median, 8 days), and mean weight was 2.2+/-0.3 kg (median, 2.2 kg). Fourteen patients weighed </=2.0 kg, and 2 patients weighed </=1.5 kg. Early mortality (death within 30 days or before hospital discharge) was 51% (34 of 67). No patient, procedural, or time-related variables correlated with increased mortality. However, there was a trend toward increased mortality with increased cardiopulmonary bypass time (P=0.076) and decreased preoperative ventricular performance (P=0.139). CONCLUSIONS: These findings suggest that low weight alone in a patient with HLHS or an anatomic variant should not be considered a contraindication to staged reconstructive surgery.

Body Weight↗

Metal compounds as tools for the construction and the interpretation of medium-resolution maps of ribosomal particles.

Procedures were developed exploiting organometallic clusters and coordination compounds in combination with heavy metal salts for derivatization of ribosomal crystals. These enabled the construction of multiple isomorphous replacement (MIR) and multiple isomorphous replacement combined with anomalous scattering medium-resolution electron density maps for the ribosomal particles that yield the crystals diffracting to the highest resolution, 3 A, of the large subunit from Haloarcula marismortui and the small subunit from Thermus thermophilus. The first steps in the interpretation of the 7. 3-A MIR map of the small subunit were made with the aid of a tetrairidium cluster that was covalently attached to exposed sulfhydryls on the particle's surface prior to crystallization. The positions of these sulfhydryls were localized in difference Fourier maps that were constructed with the MIR phases.

Animals↗

Inhaled salmeterol and fluticasone: a study comparing monotherapy and combination therapy in asthma.

BACKGROUND: The current stepwise approach to pharmacotherapy in the treatment of asthma includes the initiation of an inhaled corticosteroid with the addition of a long-acting inhaled bronchodilator if low dose inhaled corticosteroid fails to control asthma symptoms. OBJECTIVE: To determine whether initiation of salmeterol and fluticasone propionate treatment together improves asthma control greater than initiation of monotherapy with the individual agents alone with no additional safety risk in patients with asthma who had not previously been treated with inhaled corticosteroids. METHODS: A total of 136 male and female patients at least 12 years of age with asthma [forced expiratory volume in 1 second (FEV) between 50% and 80% of predicted] were randomized to twice daily salmeterol 42 microg, fluticasone propionate 88 microg, fluticasone propionate 220 microg, salmeterol 42 microg plus fluticasone propionate 88 microg, salmeterol 42 microg plus fluticasone propionate 220 microg, or placebo for 4 weeks. RESULTS: Patients treated with salmeterol combined with fluticasone propionate had improvements over baseline in FEV at endpoint that were at least twice as great (0.6 to 0.7 L) as improvements in patients treated with salmeterol (0.3 L) or fluticasone propionate alone (0.3 L) (P < .05). Patient-rated data (peak expiratory flow, asthma symptom scores, percent of days with no asthma symptoms) confirmed greater (P < .05) mean change from baseline improvements after combined treatment compared with fluticasone propionate alone. No clinically significant differences were noted between treatment groups in any safety measurement. CONCLUSION: Initiation of maintenance therapy with salmeterol and fluticasone propionate in patients with asthma treated with short-acting beta2-agonists alone provides greater improvements in pulmonary function and symptom control than initiation of maintenance therapy with fluticasone propionate alone.

Adolescent↗

The reliability of muscle biopsies taken from vastus lateralis.

The purpose of this study was to examine whether a single biopsy sample of vastus lateralis could provide an accurate estimate of capillary density (CD) which is indicative of the entire muscle, or whether capillary density is distributed unevenly and varies with muscle depth. Whole muscle cross sections of vastus lateralis were excised post mortem (n=11) for analysis of capillary density at three muscle depths, (superficial, mid and deep regions). Muscle thickness varied widely (17-79 mm) across subjects. The distribution of CD throughout the depth of the muscle was homogeneous in 8 subjects, but in 3 subjects it was heterogeneous (p<0.05). In 3 of these subjects there was a significant (p<0.05) effect of sample depth on CD. These data indicate that tissue from a single biopsy will not adequately represent the CD of the entire vastus lateralis in some individuals. Single biopsies from unspecified muscle depth, have routinely been used to estimate CD and fibre type in vastus lateralis. The present study indicates that a more reliable method of analysis would be to use the tissue from two needle biopsies taken at the superficial and deep portions of the muscle from a group of at least 10 subjects. Sampling theory analysis supported this conclusion.

Adolescent↗

Crystallographic studies on the ribosome, a large macromolecular assembly exhibiting severe nonisomorphism, extreme beam sensitivity and no internal symmetry.

Crystals, diffracting best to around 3 A, have been grown from intact large and small ribosomal subunits. The bright synchrotron radiation necessary for the collection of the higher-resolution X-ray diffraction data introduces significant decay even at cryo temperatures. Nevertheless, owing to the reasonable isomorphism of the recently improved crystals of the small ribosomal subunits, reliable phases have been extracted at medium resolution (5-6 A) and an interpretable five-derivative MIR map has been constructed. For the crystals of the large subunits, however, the situation is more complicated because at higher resolution (2.7-7 A) they suffer from substantial radiation sensitivity, a low level of isomorphism, instability of the longest unit-cell axis and nonisotropic mosaicity. The 8 A MIR map, constructed to gain insight into this unusual system, may provide feasible reasoning for the odd combination of the properties of these crystals as well as hints for future improvement. Parallel efforts, in which electron-microscopy-reconstructed images are being exploited for molecular-replacement studies, are also discussed.

Animals↗

Brompheniramine, loratadine, and placebo in allergic rhinitis: a placebo-controlled comparative clinical trial.

A double-blind, randomized, placebo-controlled, parallel-group, multicenter study was conducted to compare the effectiveness of an extended-release formulation of a classical antihistamine, brompheniramine, and a second-generation compound, loratadine, in the treatment of allergic rhinitis. Subjects with symptoms of allergic rhinitis received brompheniramine 12 mg twice daily (n = 112), loratadine 10 mg once daily (n = 112), or placebo twice daily (n = 114) for 7 days. Study medications were blinded using a double-dummy technique. Subjects completed an overall evaluation of symptom relief on a daily basis and returned on treatment days 3 and 7, at which times the investigator assessed symptom severity. The investigator and subject each completed a global efficacy evaluation, and subjects were interviewed regarding adverse experiences. The primary efficacy variable was the physicians' global efficacy evaluation on day 3. Symptoms also were analyzed as summed severity scores for all symptoms and for the nasal symptom cluster of rhinorrhea, sneezing, and nasal blockage. At all post-baseline evaluations (days 3, 7, and averaged over the two days), brompheniramine was significantly better than loratadine and placebo for both sets of summed symptom scores and all three global assessments. Loratadine was significantly better than placebo for physician ratings of total symptom severity averaged over the two days and for the physician and subject ratings of the nasal cluster on day 3. Central nervous system-related symptoms were the most frequently reported adverse experiences; somnolence was reported most frequently by patients taking brompheniramine, and its occurrence was less frequent as treatment continued. A nonprescription, extended-release formulation of brompheniramine 12 mg twice daily provided significantly better relief of symptomatic allergic rhinitis than loratadine 10 mg once daily.

Adolescent↗

Transthoracic, transdiaphragmatic excision of simultaneous lung and adrenal lesions.

Simultaneous adrenal and pulmonary lesions frequently present a therapeutic challenge to the thoracic surgeon. We describe 2 cases in which a transthoracic, transdiaphragmatic approach was used to establish tissue diagnosis and complete removal of gross tumor. In 1 case an intraoperative decision to perform a pneumonectomy was dictated by the tissue diagnosis of the adrenal mass, which was obtained with relative ease via this method. In both cases the morbidity of traditional approaches for adrenal operation was avoided.

Adrenal Gland Neoplasms↗

Emergency brain computed tomography in children with seizures: who is most likely to benefit?

OBJECTIVE: To determine whether the recently published guidelines on neuroimaging in patients with new-onset seizures are applicable to children. METHODS: We carried out a retrospective analysis of 107 neurologically normal children (excluding children with simple febrile seizures) who had undergone neuroimaging when they presented to the emergency department with a possible "first seizure." RESULTS: Eight of the 107 children had nonepileptic events (gastroesophageal reflux, syncopal event, rigor). Of the remaining 99 children, 49 had provoked seizures (complicated febrile seizure, meningo-encephalitis, toxic or metabolic abnormalities), and 50 had unprovoked seizures. A total of 19 children had brain abnormalities identified on computed tomography (CT) scan; 7 received further investigation or intervention as a result of CT scan findings (2 with tumors, 3 with vascular anomalies, 1 with cysticercosis, and 1 with obstructive hydrocephalus). CT scan abnormalities requiring treatment or monitoring were more frequently seen in children with their first unprovoked seizure (P < .01) and in those children whose seizure onset had been focal or who had focal abnormalities identified on postictal neurologic examination (P < .04). CONCLUSION: In a child, a seizure in the setting of a fever rarely indicates the presence of an unexpected CT scan lesion requiring intervention.

Adolescent↗

Broadsheet number 46: Internet for pathologists.

The Internet, and its most user-friendly manifestation, the World Wide Web (WWW), has undergone an exponential growth in the last few years. The volume of medical and pathology related information available has kept pace, making the Internet invaluable tool for the practising pathologist, supplementing traditional hard-copy textbooks and professional journals. E-mail, newsgroups, mailing lists, access to libraries, Medline, atlases, case studies and tutorials are only some of the additional features to which the net offers rapid access from your work-station. To make optimal use of electronic resources, a basic understanding of the hardware, software, communication protocols and information retrieval tools underlying the Internet is desirable. This paper is intended only as a brief introduction to what the Net has to offer to pathology in particular, and medicine in general, it is not meant to supplement the many excellent and more detailed reviews already available (see references). Parallel with the information explosion on the Net, concerns for the quality of posted material and possibility of misinformation have arisen. These issues will be addressed. Website addresses are given in parentheses in the text [e.g.: the website address of the Royal College of Pathologists of Australasia (RCPA) is given as (http:/(/)www.rcpa.edu.au/)] for easy retrieval on your Web browser. Because of the constantly evolving nature of the Web, I apologise in advance if some of the listed sites are no longer current.

Australia↗

Enlarging mediastinal mass after cardiac transplantation.

Pseudoaneurysms of the ascending aorta are a rare but potentially fatal complication of cardiac surgical procedures. There are few reports of pseudoaneurysm formation after cardiac transplantation, and previously reported cases involve mycotic aneurysmal tissue. This case report describes a 53-year-old man in whom a noninfectious aneurysm of the ascending aorta developed after cardiac transplantation.

Anastomosis, Surgical↗

Anorexia nervosa in a 7-year-old girl.

We report on a 7-year-old girl with anorexia nervosa and consider factors contributing to this early emergency. Cognitive differences in younger children can alter their understanding of this illness, so we chronicled this girl's treatment because it diverged from practices used with older patients. Accordingly, effective interventions in very young anorexics might require modifications of treatments used in postpubertal populations.

Age of Onset↗

Noninvasive assessment of language dominance in children and adolescents with functional MRI: a preliminary study.

BACKGROUND: Assessment of language organization is crucial in patients considered for epilepsy surgery. In children, the current techniques, intra-carotid amobarbital test (IAT) for language dominance, and cortical electrostimulation mapping (ESM), are invasive and risky. Functional magnetic resonance imaging (fMRI) is an alternative method for noninvasive functional mapping, through the detection of the hemodynamic changes associated with neuronal activation. We used fMRI, to assess language dominance in children with partial epilepsy. METHODS: Eleven right handed children and adolescents performed a word generation task during fMRI acquisition focused on the frontal lobes. Areas where the signal time course correlated with the test paradigm (r = 0.7) were considered activated. Extent and magnitude of signal changes were used to calculate asymmetry indices. Seven patients had IAT, ESM, or surgery outcome available for comparison. RESULTS: fMRI language dominance always agreed with IAT (6 cases) and ESM (1 case), showing left dominance in six and bilateral language in one. fMRI demonstrated left dominance in three additional children, and right dominance in one with early onset of left temporal epilepsy. Four children whose initial studies were equivocal due to noncompliance or motion artifacts were restudied successfully. CONCLUSIONS: fMRI can be used to assess language lateralization noninvasively in children. It has the potential to replace current functional mapping techniques in patients, and to provide important data on brain development.

Adolescent↗

A one-week dose-ranging study of inhaled salmeterol in children with asthma.

This was a 1-week study evaluating the safety and efficacy of two dosage regimens of salmeterol in children with asthma. A total of 243 children, aged 4-11 years, with mild-to-moderate asthma were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating salmeterol xinafoate 21 micrograms and 42 micrograms administered via metered-dose inhaler (MDI) twice daily for 1 week. Patients were allowed to use albuterol MDI as needed for relief of acute symptoms. Inhaled corticosteroids and/or cromolyn at fixed dosages could be continued during the study, but theophylline and oral beta-agonists were not allowed. Twelve-hour serial spirometry (for patients aged 6-11 years) and serial peak expiratory flow rate (PEFR) (all patients) were performed on days 1 and 8 of treatment; morning and evening PEFR were recorded each day prior to inhalation of the study drug. Safety was assessed by monitoring adverse events, clinical laboratory values, vital signs, electrocardiogram (ECG), and 24-hr ECG (Holter) monitoring. Both the 21-micrograms and 42-micrograms doses of salmeterol produced significantly greater bronchodilation, as measured by 12-hr serial forced expiratory volume in 1 sec (FEV1) (p < or = 0.02) and PEFR (p < or = 0.001), than did placebo on days 1 and 8. A small dose-response was observed, with the 42-micrograms dosage producing consistently higher serial FEV1 and PEFR than did the 21-micrograms dosage, although the differences were not statistically significant. Morning and evening PEFR increased significantly (p < or = 0.008) with both dosages of salmeterol compared with placebo. Twelve patients (5%) experienced potentially drug-related adverse events, with headache (4% in each salmeterol group) being the most common. There were no clinically significant changes in heart rate as measured by Holter monitoring, ECGs, vital signs, or clinical laboratory values following treatment with either dose of salmeterol. Salmeterol 21 micrograms or 42 micrograms twice daily was effective in producing bronchodilation in children aged 4-11 years, and both dosages had good safety profiles. Patients treated with salmeterol 42 micrograms twice daily showed a trend toward greater improvement in asthma control compared with those who received salmeterol 21 micrograms.

Administration, Inhalation↗

Survey of Ehrlichia canis antibodies among dogs in Israel.

A seroepidemiological survey was made of the prevalence of antibodies reactive with Ehrlichia canis in stray and pet dogs from five geographical regions of Israel. Serum samples from 410 dogs were assayed by an indirect fluorescent antibody test and serum reactive at a 1:20 dilution or greater was considered positive. The overall seroprevalence was 30 per cent with 23.9 per cent in pet dogs and 37.5 per cent in stray dogs. The seroprevalence in apparently healthy pets (17.6 per cent) was lower but did not differ significantly from the seroprevalence in sick animals (26.6 per cent). The seroprevalence was highest in the north of Israel and lowest in the central hilly area, and followed the same trend in both the populations sampled. Young dogs (under one year old) had a lower seroprevalence (14.9 per cent) than adult (one to eight years) (36.4 per cent) or older dogs (over eight years) (34.2 per cent). The results demonstrate that dogs in Israel are extensively exposed to E canis and indicate that ehrlichiosis is endemic in this area of the Middle East.

Animals↗

Endogenous nitric oxide and pulmonary vascular tone in the neonate.

PURPOSE: In newborns, inhaled nitric oxide (NO) has been shown to ameliorate increased pulmonary vascular resistance (PVR) precipitated by hypoxia. The role of endogenous NO production in this response is not clear. The contribution of endogenous NO to resting PVR in normoxic newborns also has not been well studied. The authors used an isolated, in situ, neonatal piglet lung-perfusion model, devoid of systemic detractors in which endogenous NO could be selectively inhibited, to determine whether (1) endogenous NO plays a role in the maintenance of PVR with normoxia, (2) endogenous NO plays a role in the response to hypoxia, and (c) inhaled NO can reverse changes induced by inhibition of endogenous NO. METHODS: Sixteen neonatal piglets underwent occlusive tracheostomy and pressure-cycled ventilation. After heparinization and ligation of the ductus arteriosus, left atrial and pulmonary arterial cannulation were performed, without ischemia, via a median sternotomy. The aorta was ligated, and lung perfusion was set at 80 mL/kg/min via an extracorporeal membrane oxygenation circuit. Hematocrit (40% to 45%), pH (7.37 to 7.44), Pco2 (35 to 40 mm Hg), and peak inspiratory pressures (20 mm Hg) were constant. Pulmonary artery pressure (PPA), left atrial pressure (PLA), and circuit flow (QPA) were recorded continuously. PVR calculated as follows: PVR[(dynes x seconds x cm(-5)) x 1,000] = [(PPA-PLA/(QPA x 1,000/60)] x 1,332. The experimental animals were ventilated with normoxic gas (FIO2, 0.21), followed by hypoxic gas (FIO2, 0.07), returned to normoxia, and then divided into two groups of eight animals each. One group remained normoxemic (FIO2, 0.21; SPA02, 100%) while the other group was made hypoxemic by ventilation with hypoxic gas (FIO2, 0.07; SPA02, 50%). Endogenous NO was suppressed with L-arginine-N-omega methyl ester (L-NAME) at 40 mg/kg in both groups. Inhaled NO was given at 40 ppm in both groups. Analysis of variance for repeated measures was used to test for statistical significance. RESULTS: Baseline normoxic PVR (3,403 +/- 1,169) was increased significantly by hypoxia (6,524 +/- 1,018, P < .01) and was fully resorted to baseline by normoxia (3,497 +/- 1,079; P = NS). In normoxic animals, inhibition of endogenous NO production by L-NAME increased PVR to levels similar to those seen during hypoxic stress (6,345 +/- 1,441, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to normoxic baseline values (3,986 +/- 1,363, P = NS). In hypoxic animals, inhibition of endogenous NO production by L-NAME also increased PVR from hypoxic baseline (9,655 +/- 1,642, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to hypoxic baseline (6,450 +/- 1,796, P = NS). CONCLUSION: In this piglet model, endogenous NO is important in the regulation of pulmonary vascular tone during both normoxia and hypoxia. Inhaled NO completely reversed the elevations in PVR caused by inhibition of endogenous NO and may normalize PVR in diseases in which the production of endogenous NO is compromised.

Administration, Inhalation↗