Celiac disease in the context of airborne allergen-associated chronic vulvo-vaginitis.

We present a woman with a three-year history of severe chronic urticaria and recurrent vulvo-vaginal Candidiasis in the setting of seasonal allergic rhinitis. Her past medical history was significant only for Bell's palsy in her childhood. Her review of systems was otherwise negative (specifically: no history of diarrhea, weight loss, malabsorption, anemia, nor eczema). Extensive testing revealed seasonal sensitivities to outdoor allergens and celiac disease. Repeating the evaluation six months after initiating a wheat-free diet, her vulvo-vaginal symptoms resolved.

Perinatal health services organization for preterm births: a multinational comparison.

OBJECTIVE: To explore population characteristics, organization of health services and comparability of available information for very low birth weight or very preterm neonates born before 32 weeks' gestation in 11 high-income countries contributing data to the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: We obtained population characteristics from public domain sources, conducted a survey of organization of maternal and neonatal health services and evaluated the comparability of data contributed to the iNeo collaboration from Australia, Canada, Finland, Israel, Italy, Japan, New Zealand, Spain, Sweden, Switzerland and UK. RESULTS: All countries have nationally funded maternal/neonatal health care with >90% of women receiving prenatal care. Preterm birth rate, maternal age, and neonatal and infant mortality rates were relatively similar across countries. Most (50 to >95%) between-hospital transports of neonates born at non-tertiary units were conducted by designated transport teams; 72% (8/11 countries) had designated transfer and 63% (7/11 countries) mandate the presence of a physician. The capacity of 'step-down' units varied between countries, with capacity for respiratory care available in <10% to >75% of units. Heterogeneity in data collection processes for benchmarking and quality improvement activities were identified. CONCLUSIONS: Comparability of healthcare outcomes for very preterm low birth weight neonates between countries requires an evaluation of differences in population coverage, healthcare services and meta-data.

Mepilex Lite dressings for the management of radiation-induced erythema: a systematic inpatient controlled clinical trial.

Erythema occurs in 80-90% of women treated for breast cancer with radiation therapy. There is currently no standard treatment for radiation-induced skin reactions. This study investigates the clinical efficacy of Mepilex Lite dressings in reducing radiation-induced erythema in women with breast cancer. A total of 28 patients were recruited; of these, 24 participants presented with 34 erythematous areas of skin for analysis. When erythema was visible, each affected skin area was randomly divided into two similar halves: one half was treated using Mepilex Lite dressings, the other half with standard aqueous cream. Skin reactions were assessed by the Radiation-Induced Skin Reaction Assessment Scale. We also evaluated any potential dose build-up by the dressings using a white water phantom, the dose distribution over the breast via thermoluminescent dosimeters (TLDs) and the surface skin temperature with an infrared thermographic scanner. Mepilex Lite dressings significantly reduced the severity of radiation-induced erythema compared with standard aqueous cream (p <0.001), did not affect surface skin temperature and caused only a small (0.5 mm) dose build-up. TLD measurements showed that the inframammary fold was exposed to significantly higher doses of radiation than any other breast region (p <0.0001). Mepilex dressings reduce radiation-induced erythema.

Nasopharygeal carcinoma in Queensland, Australia: a review of 10 years experience.

The purpose of this study was to compare the treatment outcomes of patients with nasopharyngeal carcinoma in Queensland in a 10-year period during which synchronous chemoradiotherapy has come into use and to compare characteristics of patients of different racial origins and their prognostic factors. Eighty-one patients treated between 1991 and 2001 at the Queensland Radium Institute, Brisbane, Queensland for histologically confirmed nasopharyngeal carcinoma were included. Seventeen patients were treated using the Intergroup protocol, 32 patients with miscellaneous synchronized chemoradiotherapy, 6 patients with neoadjuvant regimens and 26 patients with radiotherapy only. Asian patients were found to present earlier than White Australian patients (P < 0.02). No significant difference was identified in the histological presentation between the two ethnic groups. Asian patients were more likely to have a relapse and poor loco-regional control. Overall survival, however, was not different. Patients treated according to the Intergroup protocol had better disease-specific survival and relapse-free survival than the other groups. The median follow up was 36 months. Twenty-five patients (30%) developed recurrent disease. The 5-year salvage survival or survival after relapse was 15%. Our experience with the Intergroup protocol in our population is similar to other studies, with likelihood of improved results.

Drosophila stoned proteins regulate the rate and fidelity of synaptic vesicle internalization.

At an initial step during synaptic vesicle recycling, dynamin and adaptor proteins mediate the endocytosis of synaptic vesicle components from the plasma membrane. StonedA and stonedB, novel synaptic proteins encoded by a single Drosophila gene, have predicted structural similarities to adaptors and other proteins implicated in endocytosis. Here, we test possible roles of the stoned proteins in synaptic vesicle internalization via analyses of third instar larval neuromuscular synapses in two Drosophila stoned (stn) mutants, stn(ts) and stn(8P1). Both mutations reduce presynaptic levels of stonedA and stonedB, although stn(ts) has relatively weak effects. The mutations cause retention of synaptic vesicle proteins on the presynaptic plasma membrane but do not alter the levels or distribution of endocytosis proteins, dynamin, alpha-adaptin, and clathrin. In addition, stn(8P1) mutants exhibit depletion and enlargement of synaptic vesicles. To determine whether these defects arise from altered synaptic vesicle endocytosis or from defects in synaptic vesicle biogenesis, we implemented new methods to assess directly the efficiency of synaptic vesicle recycling and membrane internalization at Drosophila nerve terminals. Behavioral and electrophysiological analyses indicate that stn(ts), an allele with normal evoked release and synaptic vesicle number, enhances defects in synaptic vesicle recycling shown by Drosophila shi(ts) mutants. A dye uptake assay demonstrates that slow synaptic vesicle recycling in stn(ts) is accompanied by a reduced rate of synaptic vesicle internalization after exocytosis. These observations are consistent with a model in which stonedA and stonedB act to facilitate the internalization of synaptic vesicle components from the plasma membrane.

The products of the Drosophila stoned locus interact with synaptic vesicles via synaptotagmin.

The stoned locus of Drosophila melanogaster encodes two novel proteins, stonedA (STNA) and stonedB (STNB), both of which are expressed in the nervous system. Flies with defects at the stoned locus have abnormal behavior and altered synaptic transmission. Genetic interactions, in particular with the shibire (dynamin) mutation, indicated a presynaptic function for stoned and suggested an involvement in vesicle cycling. Immunological studies revealed colocalization of the stoned proteins at the neuromuscular junction with the integral synaptic vesicle protein synaptotagmin (SYT). We show here that stoned interacts genetically with synaptotagmin to produce a lethal phenotype. The STNB protein is found by co-immunoprecipitation to be associated with synaptic vesicles, and glutathione S-transferase pull-downs demonstrate an in vitro interaction between the micro2-homology domain of STNB and the C2B domain of the SYTI isoform. The STNA protein is also found in association with vesicles, and it too exhibits an in vitro association with SYTI. However, we find that the bulk of STNA is in a nonmembranous fraction. By using the shibire mutant to block endocytosis, STNB is shown to be present on some synaptic vesicles before exocytosis. However, STNB is not associated with all synaptic vesicles. We hypothesize that STNB specifies a subset of synaptic vesicles with a role in the synaptic vesicle cycle that is yet to be determined.

Embryonic expression and activity of doughnut, a second RYK homolog in Drosophila.

In the Drosophila embryo, a subset of muscles require expression and function of the RYK subfamily RTK gene derailed (drl) for correct attachment. We have isolated a second RYK homolog, doughnut (dnt), from Drosophila. The DNT protein exhibits 60% amino acid identity to DRL, and is structurally as similar to the mammalian RYK proteins as is DRL, indicating an ancient duplication event. dnt is expressed in dynamic patterns in the embryonic epidermis, being found at high level in epithelia adjacent to cells that are invaginating into the interior of the embryo, including ventral furrow, cephalic furrow, fore- and hindgut, optic lobe and tracheal pits. dnt is capable of a partial rescue of the muscle attachment defect of drl-/- embryos, indicating that it encodes a receptor with a related and significantly overlapping biochemical function.

A product of the Drosophila stoned locus regulates neurotransmitter release.

The Drosophila stoned locus encodes two novel gene products termed stonedA and stonedB, which possess sequence motifs shared by proteins involved in intracellular vesicle traffic. A specific requirement for stoned in the synaptic vesicle cycle has been suggested by synthetic genetic interactions between stoned and shibire, a gene essential for synaptic vesicle recycling (Petrovich et al., 1993). A synaptic role of stoned gene products also is suggested by altered synaptic transients in electroretinograms recorded from stoned mutant eyes (Petrovich et al., 1993). We show here that the stonedA protein is highly enriched at Drosophila nerve terminals. Mutant alleles that affect stonedA disrupt the normal regulation of synaptic vesicle exocytosis at neuromuscular synapses of Drosophila. Spontaneous neurotransmitter release is enhanced dramatically, and evoked release is reduced substantially in such stoned mutants. Ultrastructural studies reveal no evidence of major disorganization at stoned mutant nerve terminals. Thus, our data indicate a direct role for stonedA in regulating synaptic vesicle exocytosis. However, genetic and morphological observations suggest additional, subtle effects of stoned mutations on synaptic vesicle recycling. Remarkably, almost all phenotypes of stoned mutants are similar to those previously described for mutants of synaptotagmin, a protein postulated to regulate both exocytosis and the recycling of synaptic vesicles. We propose a model in which stonedA functions together with synaptotagmin to regulate synaptic vesicle cycling.

Identification of a gene family from Drosophila melanogaster encoding proteins with homology to invertebrate sarcoplasmic calcium-binding proteins (SCPS).

Using antibodies raised against the Drosophila Ca(2+)-binding protein DCABP-23, we have isolated two distinct cDNA clones that encode Ca(2+)-binding proteins of the invertebrate sarcoplasmic calcium-binding protein (SCP) family. Southern blot analysis of whole genomic DNA has shown that one of the clones, Dcabp-A.1, is present in more than one copy in the genome of the fly, and is located in the beta-heterochromatic region at cytological division 80 on chromosome III. The expression pattern of this transcript shows that it is present in the tubular but not the fibrillar muscles of the adult thorax. This expression pattern is consistent with this being a true SCP. In contrast, the expression pattern of the transcript corresponding to the second cDNA clone is exclusive to neural tissue. This transcript derives from a single copy gene, and is located at cytological position 89 D on chromosome III. Comparative analysis of the amino acid sequences from the proteins encoded by the two cDNAs with that of the original DCABP-23 protein indicates that the purified DCABP-23 contained mainly the DCABP-A.1 protein. The identification of members of the SCP family of proteins in Drosophila, will allow for a future genetic investigation of the function of these ubiquitous proteins.

A study of role ambiguity and role strain among school nurses.

Two hundred fifty-one school nurses practicing in pennsylvania were surveyed regarding perceptions of their professional role. Findings demonstrated that role ambiguity and role strain occur when school nurses attempt to practice in a setting where two disciplines, education and nursing, may have different expectations regarding role performance.

The stoned locus of Drosophila melanogaster produces a dicistronic transcript and encodes two distinct polypeptides.

The stoned gene of Drosophila melanogaster is required for normal neuronal function in both adult and larva. We have identified DNA sequences that lie within a genetic region that is known to include the stoned gene and that also reveal restriction site variations in two stoned lethal mutants. This genomic region contains a single transcription unit coding for an approximately 8.4-kb transcript. The transcript is preferentially expressed in the head of adult flies. The isolation and sequencing of cDNA and genomic clones reveals that stoned appears to encode a dicistronic mRNA, although the possible existence of other forms of mRNA cannot be excluded. Antibody cross-reactivity shows that two proteins are translated from the stoned locus in vivo. Both open reading frames (ORFs) encode novel proteins. The protein encoded by the first ORF contains four tandemly repeated motifs, and one domain of the protein encoded by the second ORF shows similarity to a family of proteins (AP50s) associated with clathrin assembly protein complexes.

Identification and characterization of two distinct calmodulin-binding sites in the Trpl ion-channel protein of Drosophila melanogaster.

Two putative light-sensitive ion channels have been isolated from Drosophila, encoded by the transient-receptor-potential (trp) and transient-receptor-potential-like (trpl) genes. The cDNA encoding the Trpl protein was initially isolated on the basis that the expressed protein binds calmodulin. Using both fusion proteins and a synthetic peptide, we now show that two calmodulin-binding sites are present in the C-terminal domain of the Trpl protein, CBS-1 and CBS-2. CBS-1 binds calmodulin in a Ca2+-dependent fashion, requiring Ca2+ concentrations above 0.3-0.5 microM for calmodulin binding. In contrast, CBS-2 binds the Ca2+-free form of calmodulin, with dissociation occurring at Ca2+ concentrations between 5 and 25 microM. Phosphorylation of a serine residue within a peptide encompassing CBS-1 by cyclic AMP-dependent protein kinase (PKA) abolishes calmodulin binding, and phosphorylation of the adjacent serine by protein kinase C appears to modulate this phosphorylation by PKA. Interpretation of these findings provides a novel model for ion-channel gating and modulation in response to changing levels of intracellular Ca2+.

Effects of quadriceps femoris muscle strengthening on crouch gait in children with spastic diplegia.

BACKGROUND AND PURPOSE: Despite evidence of weakness in children with cerebral palsy, the use of strength training in this population remains controversial. SUBJECTS: Fourteen children with spastic diplegia, ranging in age from 6 to 14 years (X = 9.1, SD = 2.5), participated in a bilateral quadriceps femoris muscle strengthening program. METHODS: The children exercised three times per week for 6 weeks using ankle weights at loads of approximately 65% of each child's maximum isotonic force production. The maximal voluntary contraction of the quadriceps femoris muscles was measured before, at the midpoint of, and immediately following the exercise program at 30, 60, and 90 degrees of knee flexion. Gait analyses were performed before and after the strengthening program to determine whether quadriceps femoris muscle strengthening influenced gait. RESULTS: Children with spastic diplegia can increase quadriceps femoris muscle strength through heavy resistance exercise. Repeated-measures analysis of variance and multivariate analysis of variance procedures were used to assess changes in force and in gait variables. Improvement in the degree of crouch at initial floor contact at the freely selected speed and an increase in stride length at free and fast speeds were found. CONCLUSION AND DISCUSSION: These findings suggest that resistance exercise is an effective treatment strategy and as such should be considered as one component in the habilitation of children with cerebral palsy.

Adolescent mothers: what factors relate to level of preventive health care sought for their infants?

This exploratory study investigated the level of preventive health care services that adolescent mothers (ages 14 to 17) sought for their infants during the first 2 years of the infants' lives. Findings showed that mothers who maintained a relationship with their child's father or exhibited a high Powerful Others Locus of Control were more likely to practice better preventive health care. The role that social support and locus of control play in mediating parental stress is discussed. Implications for nurses working with adolescent mothers are presented.

PIP: Consistent with the trend in adolescent parenting research toward a focus on intragroup differences rather than comparisons of adolescent mothers with their older counterparts, this study developed psychosocial profiles associated with differing levels of infant care. Specifically, measures of perceived social support, health locus of control, and parenting stress were correlated with the preventive health care obtained for the infants of 49 teen mothers (ages 14-17 years) recruited from a US well-child clinic. 39 mothers were Black and 8 were Hispanic; all were public assistance recipients. The average maternal age at delivery was 15.5 years; the infants' ages ranged from 12 to 18 months at the time of the study. There was considerable variability in compliance with recommended clinic visits, and the number of missed appointments ranged from 0 to 10. 40% of infants received the recommended one-month visit and 67% received their first immunization on time; by 15 months, however, over a third of the infants were behind on their immunization schedule. Only 10% of the variance in health care compliance patterns was explained by the locus of control, stress, and social support variables. On the other hand, teen mothers who still maintained a relationship with the infant's father accessed significantly higher levels of preventive child health care. Also positively associated with preventive care was a high "powerful other" locus of control score. Parenting-related stress was inversely associated with perceived adequate support networks. Nurses who work with adolescent mothers are urged to facilitate the mobilization of internal and external resources required to adapt to the stress inherent in the role transition to parenting.

The Age Group Evaluation and Description (AGED) Inventory: a new instrument for assessing stereotypes of and attitudes toward age groups.

The AGED Inventory was designed to overcome shortcomings identified in the Aging Semantic Differential, a frequently used measure of how age groups are perceived. The new instrument was developed to allow assessment both of age stereotypes and of attitudes toward age-specified targets. The Inventory was developed with data from 300 male and 300 female respondents. Two seven-item evaluative factors (the Goodness and Positiveness dimensions) resulted from a series of factor analyses used to reduce an initial set of thirty-five evaluative adjective pairs. Two seven-item descriptive factors (the Vitality and Maturity dimensions) resulted from a separate series of factor analyses used to reduce an initial set of fifty adjective pairs judged to differentiate age groups. Using confirmatory factor analyses and coefficients of congruence on data from an additional 800 respondents, the factor structures of the two evaluative factors and of the two descriptive factors were found to be replicable for young, middle-aged, and old targets assessed in either between or within subject designs. Its ease of administration, multidimensionality, flexibility of targets specification, and capability for assessing attitude and/or stereotype in a manner congruent with current conceptualizations of these constructs make the AGED Inventory useful in a variety of contexts.

A neural gene from Drosophila melanogaster with homology to vertebrate and invertebrate glutamate decarboxylases.

Cross-species hybridization has been used to isolate a second Drosophila gene, with homology to a feline glutamate decarboxylase (Gad) cDNA. The gene differs in sequence, chromosomal location, and spatial expression from the previously reported Drosophila Gad gene, but both encode proteins of 58 kDa. The derived amino acid sequence reveals a typical pyridoxal phosphate binding site and sequence homology consistent with a glutamate decarboxylase function. The protein includes an amino-terminal polyasparagine sequence, and a beta-pleated sheet region, with regularly spaced glutamine and arginine residues, not found in other decarboxylases. Expression in the adult is limited to the neuropil of the first optic ganglion and to regions of the thoracic musculature that may correspond to the location of motor neuron axons. This is consistent with a glial localization for the transcript. There is no overlap with the reported expression of Drosophila Gad. Although the molecular evidence suggests that this gene encodes a pyridoxal phosphate-dependent decarboxylase, glutamate decarboxylase activity associated with this gene could not be demonstrated, and the in vivo substrate is unknown. It is possible that the protein encoded by this gene is novel, not only in sequence and spatial expression, but also in substrate specificity.

Cyromazine resistance in Drosophila melanogaster (Diptera: Drosophilidae) generated by ethyl methanesulfonate mutagenesis.

Flies resistant to cyromazine (CGA-72662) were selected in susceptible laboratory populations of Drosophila melanogaster (Meigen) treated with ethyl methane-sulfonate after growth on cyromazine concentrations > LC99. Two resistant lines were obtained. In each case, resistance was a result of a mutation in a single, but different, gene. The resistance genes, designated Rst(2)Cyr and Rst(3)Cyr, were localized to map positions 64 on chromosome II and 47 on chromosome III, respectively. Concentration-mortality analysis of each mutant revealed that both genes conferred a low level (< 5 times) of resistance to cyromazine. Rst(2)Cyr produced LC99s of 1.3 x 10(-4)% (wt/vol) for heterozygotes and 2.7 x 10(-4)% for homozygotes; Rst(3)Cyr values were 1.6 x 10(-4) and 1.8 x 10(-4)%, respectively. These values compare with an LC99 of 5 x 10(-5)% for wild-type. The role of D. melanogaster as a model for insecticide resistance studies is discussed, especially the comparison of laboratory-generated cyromazine resistance in D. melanogaster with field resistance in Musca domestica L.

A genetic analysis of the stoned locus and its interaction with dunce, shibire and Suppressor of stoned variants of Drosophila melanogaster.

The genetic complementation patterns of both behavioral and lethal alleles at the stoned locus have been characterized. Mosaic analysis of a stoned lethal allele suggests that stoned functions either in the nervous system or in both the nervous system and musculature, but is not required for gross neural development. The behavioral alleles stnts and stnC, appear to be defective in a diametrically opposite sense, show interallelic complementation, and indicate distinct roles for the stoned gene product in the visual system and in motor coordination. A number of other neurological mutations have been investigated for their possible interaction with the viable stoned alleles. Mutations at two loci, dunce and shibire, act synergistically with the stnts mutations to cause lethality, but fail to interact with stnC. A third variant (Suppressor of stoned) has been identified which can suppress the debilitation associated with the stnts mutations. These data, together with a previously identified interaction between the stnts and tan mutants, indicate a central role for the stoned gene product in neuronal function, and suggests that the stoned gene product interacts, either directly or indirectly, with the neural cAMP second messenger system, with the synaptic membrane recycling pathway via dynamin, and with biogenic amine metabolism.

Identification of a Drosophila gene encoding a calmodulin-binding protein with homology to the trp phototransduction gene.

We have isolated a number of Drosophila cDNAs on the basis of their encoding calmodulin-binding proteins. A full-length cDNA clone corresponding to one of these genes has been cloned and sequenced. Conservation of amino acid sequence and tissue-specific expression are observed between this gene and the transient receptor potential (trp) gene. We propose the name transient receptor potential-like (trpl) to describe this newly isolated gene. The trpl protein contains two possible calmodulin-binding sites, six transmembrane regions, and a sequence homologous to an ankyrin-like repeat. Structurally, the trpl and trp proteins resemble cation channel proteins, particularly the brain isoform of the voltage-sensitive Ca2+ channel. The identification of a protein similar to the trp gene product, yet also able to bind Ca2+/calmodulin, allows for a reinterpretation of the phenotype of the trp mutations and suggests that both genes may encode light-sensitive ion channels.