Clinical testing results and high patient satisfaction with a new needle-free device for growth hormone in young children.

Fifty children ages 4-10 yr with type 1 diabetes mellitus volunteered to participate in a study to evaluate and compare a new needle-free device developed for growth hormone delivery. Children answered descriptive questions related to nervousness and worry, hurt or pain, redness or bleeding, and stinging and wetness. Choices for answers for each of these five questions were none, a little, or a lot. None or a little was also combined to give a minimal category. Children also answered four questions that compared the needle-free device to their morning insulin needle injection in reference to ease of use, pain, nervousness, and overall preference. Half the children had single comfort rings inserted to increase the injection pressure. Results indicated no difference in question responses with or without pressure rings. Pain (92%), erythema (96%), worry (90%), stinging (86%) and wetness (96%) were minimal and significant (0.001 > p < 0.03) following all questions. Results of the comparative questionnaire indicated that the device was easier (p < 0.03) to use than needles and significantly preferred (p < 0.001) in 74% of children under age 10.

Possible consequences of social drinking in the early stages of Alzheimer disease.

Although research supports the idea that alcohol is not a risk factor for developing Alzheimer disease (AD), surprisingly little attention has been given to the role of social drinking in the early stages of the disorder. The current review highlights potential alcohol- and disease-related interactions on neurologic, cognitive, and behavioral functioning in individuals experiencing the early stages of AD. Understanding how alcohol interacts with AD can benefit both treatment providers (eg, interpreting clinical tests) and caregivers (eg, managing disruptive behaviors) by providing important clues to potentially reversible impairments that may negatively affect the everyday functioning of individuals with the disorder.

Sharing of culture: adult grandchildren's perceptions of intergenerational relations.

The current study addressed the sharing of traditions, beliefs, and customs (i.e., culture) between grandparents and grandchildren. Two hundred and forty-six adult grandchildren were surveyed on both existing and newly created measures of grandparenting. Results indicated that extent of shared activities, attitudes toward grandparents, and perceptions of cultural sharing were significantly related. Additionally, it was found that minority and female participants were more likely to engage in intergenerational culture sharing and reported more positive statements about this sharing in response to open-ended questions. Findings highlights the importance of cultural sharing to perceptions of grandchild-grandparent relationships.

Burns and fractures.

When burn injury and skeletal trauma are two components of the multiple trauma injury, specific difficulties arise requiring a constant reevaluation of risks and benefits for each planned therapeutic maneuver. Unfortunately there is a scarcity of published literature that addresses this specific topic. This article focuses on these issues and discusses the therapeutic options available. The object of this article is to summarize available information, and offer recommendations to assist the clinician in treating this challenging clinical problem.

Probing the contribution of internal cavities to the volume change of protein unfolding under pressure.

The structural origin of the decrease in system volume upon protein denaturation by pressure has remained a puzzle for decades. This negative volume change upon unfolding is assumed to arise globally from more intimate interactions between the polypeptide chain and water, including electrostriction of buried charges that become exposed upon unfolding, hydration of the polypeptide backbone and amino acid side chains and elimination of packing defects and internal void volumes upon unfolding of the chain. However, the relative signs and magnitudes of each of these contributing factors have not been experimentally determined. Our laboratory has probed the fundamental basis for the volume change upon unfolding of staphylococcal nuclease (Snase) using variable solution conditions and point mutants of Snase (Royer CA et al., 1993, Biochemistry 32:5222-5232; Frye KJ et al., 1996, Biochemistry 35:10234-10239). Our prior results indicate that for Snase, neither electrostriction nor polar or nonpolar hydration contributes significantly to the value of the volume change of unfolding. In the present work, we investigate the pressure induced unfolding of three point mutants of Snase in which internal cavity size is altered. The experimentally determined volume changes of unfolding for the mutants suggest that loss of internal void volume upon unfolding represents the major contributing factor to the value of the volume change of Snase unfolding.

Structural characterization of the pressure-denatured state and unfolding/refolding kinetics of staphylococcal nuclease by synchrotron small-angle X-ray scattering and Fourier-transform infrared spectroscopy.

The pressure-induced unfolding of wild-type staphylococcal nuclease (Snase WT) was studied using synchrotron X-ray small-angle scattering (SAXS) and Fourier-transform infrared (FT-IR) spectroscopy, which monitor changes in the tertiary and secondary structural properties of the protein upon pressurization. The experimental results reveal that application of high-pressure up to 3 kbar leads to an approximate twofold increase of the radius of gyration Rg of the native protein (Rg approximately 17 A) and a large broadening of the pair-distance-distribution function, indicating a transition from a globular to an ellipsoidal or extended chain structure. Analysis of the FT-IR amide I' spectral components reveals that the pressure-induced denaturation process sets in at 1.5 kbar at 25 degrees C and is accompanied by an increase in disordered and turn structures while the content of beta-sheets and alpha-helices drastically decreases. The pressure-induced denatured state above 3 kbar retains nonetheless some degree of beta-like secondary structure and the molecule cannot be described as a fully extended random coil. Temperature-induced denaturation involves a further unfolding of the protein molecule which is indicated by a larger Rg value and significantly lower fractional intensities of IR-bands associated with secondary-structure elements. In addition, we have carried out pressure-jump kinetics studies of the secondary-structural evolution and the degree of compactness in the folding/unfolding reactions of Snase. The effect of pressure on the kinetics arises from a larger positive activation volume for folding than for unfolding, and leads to a significant slowing down of the folding rate with increasing pressure. Moreover, the system becomes two-state under pressure. These properties make it ideal for probing multiple order parameters in order to compare the kinetics of changes in secondary structure by pressure-jump FT-IR and chain collapse by pressure-jump SAXS. After a pressure jump from 1 bar to 2.4 kbar at 20 degrees C, the radius of gyration increases in a first-order manner from 17 A to 22.4 A over a timescale of approximately 30 minutes. The increase in Rg value is caused by the formation of an extended (ellipsoidal) structure as indicated by the corresponding pair-distance-distribution function. Pressure-jump FT-IR studies reveal that the reversible first order changes in beta-sheet, alpha-helical and random structure occur on the same slow timescale as that observed for the scattering curves and for fluorescence. These studies indicate that the changes in secondary structure and chain compactness in the folding/unfolding reactions of Snase are probably dependent upon the same rate-limiting step as changes in tertiary structure.

The kinetic basis for the stabilization of staphylococcal nuclease by xylose.

The effect of xylose on the rates of folding and unfolding of staphylococcal nuclease (nuclease) have been investigated using fluorescence-detected pressure-jump relaxation kinetics in order to establish the kinetic basis for the observed stabilization of nuclease by this sugar (Frye KJ, Perman CS, Royer CA, 1996, Biochemistry 35:10234-10239). The activation volumes for both folding and unfolding and the equilibrium volume change for folding were all positive. Their values were within experimental error of those reported previously (Vidugiris GJA, Markley JL, Royer CA, 1995, Biochemistry 34:4909-4912) and were independent of xylose concentration. The major effect of xylose concentration was to increase significantly the rate of folding. The large positive activation volume for folding was interpreted previously as indicating that the rate-limiting step in nuclease folding involves dehydration of a significant amount of surface area. A large effect of xylose on the rate constant for folding provides strong support for this interpretation, because xylose, an osmolyte, stabilizes the folded state of proteins through surface tension effects. These studies further characterize the transition state in nuclease folding as lying closer to the folded, rather than the unfolded state along the folding coordinate in terms of the degree of burial of surface area. The image of the transition state that emerges is consistent with a dry molten globule.

An unusual mechanism of burn injury due to flaming drinks.

Bars and cocktail lounges serve various forms of flaming drinks, usually made with very high-proof alcohol. The drinks are lit and then served. If additional alcohol from the bottle is added to a still-burning drink, flames may spread up the stream of alcohol into the bottle and cause a flash of flame out the bottle's neck. Injuries can require grafting. Three cases are reported. A 32-year-old white female sustained burns covering 10 per cent of her body surface, including the face. Surgery with split-thickness grafts were required. Pressure garments were prescribed for 6 months. A 34-year-old black female was burned by a "volcano" drink. Burns covered 20 per cent of her body surface, including the face. Split-thickness grafts were required on multiple occasions. Infected wounds healed slowly. Reconstructive surgery has so far required eight procedures. A 39-year-old white male sustained severe burns to 10 per cent of his body, including the face. Grafting was carried out. Pressure garments were required. Permanent visible facial scarring is present in all three cases. This type of accident is readily preventable.

Impairments of number processing induced by prenatal alcohol exposure.

Prenatal alcohol exposure causes a variety of cognitive deficits, notably in mathematics and higher order processes such as abstraction. An exploratory battery was developed to examine specific types of number processing impairments in 29 adolescent and adult patients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) relative to controls matched for age, gender, and educational level. The battery included 11 tests: number reading and writing, exact calculation (addition, multiplication, subtraction), approximate calculation (selecting a plausible result for an operation), number comparison, proximity judgment, and cognitive estimation. The results indicated particular difficulties in calculation and estimation tests, with intact number reading and writing ability. The greatest impairment was found in the cognitive estimation test, which is sensitive to frontal lobe lesions. The patterns of deficit described may reflect either the diffuseness of brain damage incurred from prenatal alcohol exposure, or a cumulative deficit in comprehension which may be important for the acquisition of higher-order mathematical abilities.

Simulated biologic intelligence used to predict length of stay and survival of burns.

From July 13, 1988, to May 14, 1995, 1585 patients with burns and no other injuries besides inhalation were treated; 4.5% did not survive. Artificial neural networks were trained on patient presentation data with known outcomes on 90% of the randomized cases. The remaining cases were then used to predict survival and length of stay in cases not trained on. Survival was predicted with more than 98% accuracy and length of stay to within a week with 72% accuracy in these cases. For anatomic area involved by burn, burns involving the feet, scalp, or both had the largest negative effect on the survival prediction. In survivors burns involving the buttocks, transport to this burn center by the military or by helicopter, electrical burns, hot tar burns, and inhalation were associated with increasing the length of stay prediction. Neural networks can be used to accurately predict the clinical outcome of a burn. What factors affect that prediction can be investigated.

Testing the correlation between delta A and delta V of protein unfolding using m value mutants of staphylococcal nuclease.

The application of hydrostatic pressure to aqueous protein solutions results in the unfolding of the protein structure because the protein-solvent system volume is smaller for the unfolded state. Contributions to this decrease in volume upon unfolding (delta Vu) derive from altered interactions of the protein with solvent and are presumed to include electrostriction of charged residues, elimination of packing defects, and hydration of hydrophobic surfaces upon unfolding. If the contribution of hydrophobic surface area solvation to the observed volume change of unfolding were large and negative, as is generally assumed, then one would expect to find a correlation between the amount of surface area exposed on unfolding, delta A(u), and the volume change, delta Vu. In order to test this correlation, we have determined delta Vu for two mutants of staphylococcal nuclease, A69T + A90S and H121P, whose unfolding by denaturant is, respectively, either significantly more (28%) or significantly less (28%) cooperative than that observed for wild-type (WT). This cooperativity coefficient or m value has been shown to correlate with delta A(u). If, in turn, delta Vu is correlated with delta A(u), we would expect the m+ mutant, A69T + A90S, to exhibit a delta Vu that is more negative than WT nuclease, while the delta Vu for the m- mutant, H121P, should be smaller in absolute value. To verify the correlation between m value and delta A(u) for these mutants, we determined the xylose concentration dependence of the stability of each mutant at atmospheric pressure and as a function of pressure. The efficiency of xylose stabilization was found to be much greater for the m+ mutant than for WT, consistent with an increase in delta A(u), while that of the m- mutant was found to be only slightly greater than for WT, indicating that other factors may contribute to the denaturant m value in this case. Regardless of the denaturant m value or the effect of xylose on stability, the volume changes upon unfolding for both mutants were found to be within error of that observed for WT. Thus, there does not appear to be a correlation between the volume change and the change in exposed surface area upon unfolding. We have previously shown a lack of pH dependence of the volume change, ruling out electrostriction as a dominant contribution to delta Vu of nuclease. These studies implicate either compensation between polar and nonpolar hydration or excluded volume effects as the major determinant for the value of delta Vu.

Incidence and correlates of breast-feeding in socioeconomically disadvantaged women.

Although the incidence of breast-feeding has more than doubled in the United States in recent years, this increase has been less evident among blacks and in lower socioeconomic groups. To understand better this lower incidence, cognitive and personality correlates of breast-feeding were examined in two independent lower-class samples: 137 black inner-city mothers and 50 predominantly white mothers. Ego development, depression, and verbal competence were assessed during the first postpartum year. Only 21.9% of the black sample chose to breast-feed, in contrast with 58.0% of the white sample. Although unrelated to depression and social support, breast-feeding was positively associated with ego level and cognitive ability in both samples. Cognitive ability was assessed using the Peabody Picture Vocabulary Test-Revised, which was found to be valid in relation to maternal and infant characteristics for the black socially disadvantaged sample. When compared using multiple regression analysis, the relation of ego maturity to breast-feeding was generally stronger than that of cognitive ability. Women with more ego maturity may breast-feed because of increased feelings of empathy or nurturance or because they are more attuned to current health advisories and able to deviate from community norms to adopt breast-feeding practices more characteristic of the white middle class.

Effect of maternal social support on attachment: experimental evidence.

The present study used an experimental format to evaluate the influence of maternal social support on the development of attachment. 46 WIC primigravidas were randomly assigned to an experimental or control condition. Volunteer coaches, trained to provide maternal support and information, met with experimentals prenatally and during the first postpartum year. Experimentals and controls did not differ on demographics, ego level, verbal ability, affect, or perceived social support. At 14 months, experimental infants scored higher on an Attachment Ratings cluster from Waters and Deane's new Q-sort procedure. This cluster was more sensitive than a Criterion Sort measure in detecting the effect of the manipulation and as or more sensitive to maternal affect, perceived support, and the HOME. These findings provide experimental evidence regarding the importance of social support on infant attachment and support for an alternative approach for reducing data from the attachment Q-sort.

Torulopsis glabrata urinary infections: a review.

During a 12-year prospective period 9 referral patients were treated for proved Torulopsis urinary infections. Of the 9 patients 7 had irritative voiding symptoms and pyuria was present in 8. To estimate incidence of infection, a retrospective review was performed between January 1982 and December 1983. A total of 105 urine specimens from 57 hospitalized patients yielded Torulopsis glabrata. Two patients suffered symptomatic invasive infections. Patients were treated with antifungal therapy only when invasive symptomatic infections persisted despite elimination of predisposing factors. 5-Fluorocytosine eradicated Torulopsis funguria in 4 of 6 patients in whom it was used. Prolonged therapy with ketoconazole was also successful. Surgical removal of associated stones or fungal coagulum was sometimes required.

Successful transurethral drainage of bilateral seminal vesicle abscesses.

We report the successful management of bilateral seminal vesicle abscesses with transurethral unroofing and drainage of the abscess cavities. The diagnosis was confirmed by computerized tomography. Transurethral drainage became necessary after percutaneous drainage had proved to be inadequate.