Synthesis of thymosin α1 by fragment condensation using tert.-butyl side chain protection

A novel synthesis of thymosin α₁ by classical methods using seven tert. -butyl side chain protected fragments is described. Optimum conditions were found for the final DCC/HOBt coupling of the two key intermediates; decapeptide and octadecapeptide. Thymosin α₁ was purified by two stages of preparative HPLC (partial purification with C₈ and final purification with C₁₈ reverse phase silica gel) to give a 30% overall yield for the final four stages of synthesis (including catalytic hydrogenation of octadecapeptide, coupling, deprotection and purification). The product was shown to be homogeneous by thin-layer and paper high voltage electrophoresis, isoelectric focusing analysis, thin-layer chromatography and high performance liquid chromatography. Amino acid analysis, optical rotation, ¹ H-n.m.r. spectroscopy, FAB mass spectroscopy and peptide mapping after tryptic digestion confirmed the structure of thymosin α₁. Three minor stereoisomer contaminants were isolated by HPLC and characterized as [D-Lys¹⁴]-thymosin α₁, [D-Lys¹⁷]-thymosin α₁ and [D-Ala³]-thymosin α₁ resulting from racemization at Lys¹⁴, Lys¹⁷ and Ala³ during the coupling of the fragments. A final contaminant, isolated by HPLC, was characterized as N^α-isobutyloxycarbonyl-thymosin α₁ (15–28), which results from “wrong way opening” of an activated mixed anhydride.     

Sequelae of Haemophilus influenzae meningitis

Fourteen children who had had Haemophilus influenzae meningitis more than two years earlier have been compared with their siblings. WISC, Frostig and Bender psychological tests and neurological examination were performed so that subject/sibling differences could be analysed. On neurological examination, subjects overall performed worse than the controls, although no "hard" neurological signs were found. Prolonged fever during the meningitis was associated with poorer results in psychological tests. In the subjects, there was a significant increase in left lateral dominance which may have been due to brain damage by the meningitis. However, most subjects did not differ significantly from their siblings in the tests, suggesting that prompt and adequate treatment of bacterial meningitis can prevent sequelae.     

Stability and decline in gross motor function among children and youth with cerebral palsy aged 2 to 21 years

This paper reports the construction of gross motor development curves for children and youth with cerebral palsy (CP) in order to assess whether function is lost during adolescence. We followed children previously enrolled in a prospective longitudinal cohort study for an additional 4 years, as they entered adolescence and young adulthood. The resulting longitudinal dataset comprised 3455 observations of 657 children with CP (369 males, 288 females), assessed up to 10 times, at ages ranging from 16 months to 21 years. Motor function was assessed using the 66-item Gross Motor Function Measure (GMFM-66). Participants were classified using the Gross Motor Function Classification System (GMFCS). We assessed the loss of function in adolescence by contrasting a model of function that assumes no loss with a model that allows for a peak and subsequent decline. We found no evidence of functional decline, on average, for children in GMFCS Levels I and II. However, in Levels III, IV, and V, average GMFM-66 was estimated to peak at ages 7 years 11 months, 6 years 11 months, and 6 years 11 months respectively, before declining by 4.7, 7.8, and 6.4 GMFM-66 points, in Levels III, IV, and V respectively, as these adolescents became young adults. We show that these declines are clinically significant.     

The use of Roy's adaptation model applied to a patient with breast cancer

Roy's adaptation model provides a framework for holistic oncology nursing practice. In this article an overview of Roy's model is provided, and the model is applied to a patient with breast cancer for an assessment of behaviour and the stimuli influencing behaviour, and for the planning and evaluation of nursing care. Also, a comprehensive list of nursing diagnoses is categorized according to Roy's four adaptive modes.     

Steroid-Eluting Epicardial Pacing Electrodes: Six Year Experience of Pacing Thresholds in a Growing Pediatric Population

Indications for pacemaker implantation in the pediatric population often include sinus or atrioventricular node dysfunction following surgery for congenital heart defects. However, patient size, cardiac defects, and vascular and valvular concerns may limit transvenous lead utilization. Since the epicardial surface of these patients often exhibits variable degrees of fibrosis from scar tissue formation or pericardial adhesions, chronic low output (2.5/1.6 V, 0.3 ms) epicardial pacing from implant is not currently recommended in children due to frequent threshold changes and electrode exit block. As a result, pacing in children is often viewed as a less efficient system than in adults. The addition of steroid combined with newer low threshold electrode designs however stabilizes the electrode-tissue interface and eliminates postimplant changes seen with standard smooth surface electrodes potentially permitting efficient chronic pacemaker application to all patient ages. The stability of chronic low output epicardial pacing with steroid-eluting electrodes was prospectively studied in 22 patients (ages 2 days-18.5 years, median 3.5 years) for up to 6 years. Chronic pulse width thresholds were compared according to implant site and association of prior cardiac surgery. A total of 26 pacing leads were implanted. The acute implant mean pulse width threshold (2.5 V) for all the electrodes studied was 0.10 ms ± 0.05 ms. Stable low thresholds were maintained for up to 6 years without significant variation from implant. Mean ventricular pulse width thresholds (0.12 ms ± 0.05 ms) were significantly higher (P < 0.001) than atrial thresholds (0.06 ms ± 0.03 ms) at implant and throughout the study period. The thresholds in the patients following cardiac surgery were comparable to those without previous cardiac surgery (P = NS). Stable low thresholds may be chronically maintatined for up to 6 years for epicardial steroid-eluting electrodes irrespective of pacing site or associated cardiac surgery.     

Dieting Status and its Relationship to Eating and Physical Activity Behaviors in a Representative Sample of US Adolescents

Objective To determine whether adolescents engaging in extreme weight loss methods (ie, vomiting and diet pills) and those using more moderate methods differ from each other in dietary intake (fruits, vegetables, and higher-fat foods) and physical activity, and to compare these variables in dieting and nondieting adolescents.Design Data were obtained from the 1993 Youth Risk Behavior Survey.Subjects/settings The survey was administered to a nationally representative sample of 16,296 adolescents in grades 9 through 12 in a school setting.Statistical analyses Data were analyzed for 16,125 adolescents. Associations between weight control behaviors and dietary intake and physical activity were examined using mixed-model logistic regressions, controlling for grade in school, race, parental education, region of the country, and urban vs nonurban residence.Results Differences in dietary and physical activity were found among adolescents who use extreme weight loss methods and moderate methods, and between dieters and nondieters. Adolescents using moderate methods of weight control engaged in more health-promoting eating and exercise behaviors than did extreme dieters or nondieters. Girls categorized as extreme dieters were less likely to eat fruits and vegetables than were moderate dieters (odds ratio [OR]=.56) or nondieters (OR=.75), and were more likely than more moderate dieters (OR=.76) to have consumed 2 or more servings of high-fat foods during the previous day.Applications/conclusions Our findings suggest the importance of distinguishing between different types of dieting behaviors in clinical settings and research studies. Adolescents engaging in extreme weight control behaviors may be at particular risk for inadequate nutritional intake. In contrast, adolescents using more moderate methods may be consuming a more healthful diet than are nondieters. For all adolescents, nutrition guidance on healthful and safe weight control strategies is needed. J Am Diet Assoc. 1998;98:1127–1132,1135.     

Olestra Postmarketing Surveillance Study: Design and Baseline Results from the Sentinel Site

Objective To describe the design of the Olestra Postmarketing Surveillance Study (OPMSS) and to present baseline results from the sentinel site. The purpose of the OPMSS is to monitor consumption patterns of olestra-containing snacks and to determine whether consumption affects nutritional status.Design The OPMSS combines repeated cross-section, random-digit dial telephone surveys before and after the market release of olestra-containing foods as well as intensive dietary and clinical assessments on a subsample of survey participants.Subjects Data are from baseline telephone (n=1,962) and clinical (n=1,069) assessment of participants (aged 18 to 74 years) in the Marion County, Indiana, sentinel site. Mean age of participants in the telephone survey was 43.2 years; 19% of respondents were black and 29% had completed college.Statistical analysis Analyses examined associations among savory snack use, fruit and vegetable consumption, and demographic and health-related characteristics. Data from the telephone survey were adjusted to be representative of the Marion County population.Results Almost 96% of the population surveyed had eaten savory snacks in the month before the survey: 74% had eaten regular-fat, 26% fat-reduced, and 78% nonfat types. Total snack consumption did not differ by gender, education, or race. Residents younger than 35 years ate snacks 16 times a month compared with 12 times a month among older residents. Types of snacks consumed differed markedly by demographic characteristics. Male, younger, and less educated residents ate more regular-fat snacks; female, white, and college-educated residents ate more nonfat snacks. In general, residents practicing healthful behaviors, including not smoking, eating fruits and vegetables, and exercising, also ate fewer regular-fat and more nonfat snacks. Fat intake was also related linearly to use of snack foods, ranging from 33.2% of energy among those consuming 1 serving per month or less to 36.8% among those consuming 20 or more servings per month.Applications/conclusions Procedures for recruitment and nutrition assessment appear adequate for evaluating the impact of olestra consumption on nutritional status. Nutritionists should be aware that there is potential for relatively high olestra consumption, given that almost 35% of Marion County residents eat snack foods at least 20 times a month. Consumers eating at least 20 servings of snacks per month derived more than 12% of their total energy and fat from snack foods, which suggests that substituting olestra snacks could substantially reduce intakes of fat and energy. J Am Diet Assoc. 1998;98:1290–1296.     

Inhibition of brain cell excitability by lidocaine,QX314, and tetrodotoxin: a mechanism for analgesia from infused local anesthetics?

Local anesthetic infusions have been used to provide analgesia in a variety of painful conditions. The mechanism for this drug effect remains unknown. To better define the electrical effects of lidocaine concentrations comparable to those obtained during analgesic infusions, lidocaine (0.05-3 mmol l^-1), QX314 (an obligatorily charged, quaternary lidocaine derivative applied within the cells), and tetrodotoxin (10 nmoll^-1) were applied to rat hippocampal pyramidal cells. The three drugs, which inhibit Na⁺ currents by varying mechanisms, produced tonic increases in (firing) current threshold, and decreases in the amplitude of action potentials measured using an intracellular microelectrode technique. Lidocaine inhibited action potential spikes and increased current threshold in a concentration-dependent fashion. Lidocaine 50 and 100 μmol 1^-1 did not inhibit action potentials, but increased firing threshold by nearly 100%. Lidocaine 1–3 mmol l^-1 significantly inhibited action potential amplitude and increased threshold by as much as 800%. Similarly, QX314 and tetrodotoxin produced greater increases in current threshold than in action potential amplitude. QX314 produced phasic (or frequency-dependent) block during trains of stimuli at 1 Hz, even when almost no tonic block was present. Lidocaine produced less phasic block than QX314, and required both greater tonic block and more frequent stimulation to produce the phenomenon. Tetrodotoxin demonstrated no phasic block. Increases in current threshold occurred in lidocaine concentrations associated with analgesia and toxicity; inhibition of action potentials occurred scarcely at all at these concentrations. Thus, tonic increases in current threshold may underlie analgesia and supplementation of general anesthesia by intravenous lidocaine.     

A Nurse Establishes Prenatal at Med-School Clinic

Prenatal services at an outpatient OB clinic on the Pacific Coast were greatly improved by a Perinatal Clinical Nurse Specialist. Among the objectives she formulated and implemented were better patient access to care, prenatal classes, personalized patient care and education, in service education for staff nurses and improved education for nursing students, better utilization of nursing time, and a more efficient clinic structure. She also helped to devise new forms for diet histories, public health department referrals, and a Maternal-Child Nursing Assessment Care Plan. The forms are included with the article.     

The Needs of Families of Infants Discharged Home with Continuous Oxygen Therapy

Forty-four parents of 48 infants who had been discharged home with continuous oxygen therapy described their experiences, needs, and resources in a semistructured interview. In addition, 20 professionals in contact with these infants were interviewed to determine their perceptions of discharge preparations, teaching, relief care, coordination of medical care, and expertise of community professionals regarding high-risk infants on oxygen. Both the professionals and parents reported a need for improved discharge teaching and community support services. Researchers concluded that individual needs must be considered in arranging supportive interventions, as needs vary across families, time, and geographic locations.