Profiles of adolescent stress: the development of the adolescent stress questionnaire (ASQ).

The importance of stress in the understanding of adolescent health and well-being is widely documented. The measurement of adolescent stress has however been subjected to sufficient methodological and conceptual criticism in recent times to warrant a concerted re-evaluation of the exercise. This study sought information on the nature of adolescent stressors, building on a previous instrument developed by the first author to ask adolescents themselves to inform the development of a pool of new items reflecting stressor experience and to advise on the wording of these items to comprehensively assess that experience. This pool of items was then administered as a self-reported questionnaire to a large sample of school-age adolescents (N>1000) together with a scale to assess the intensity of distress arising from stressor occurrence. Principal components analysis of the questionnaire yielded 10 internally reliable dimensions of adolescent stress, the nature of which were consistent with the available literature on adolescent stressor experience. Scales constructed from this PCA related positively to measures of anxiety and depression, and negatively to a measure of self-esteem, suggesting that they were valid measures of adolescent stress. Test-retest reliability was good for all scales. The resultant Adolescent Stress Questionnaire (ASQ) is therefore suggested to have potential for the measurement of adolescent stress in both research and clinical contexts.

Pemphigus vulgaris: clinicopathologic review of 33 cases in the oral cavity.

A retrospective study was conducted on all cases of pemphigus vulgaris occurring on oral mucosal surfaces in the files of the Oral Pathology Laboratory at Temple University from 1974 to 1996. A total of 35 biopsies from 33 patients were reviewed, 25 female and eight male. Patient ages ranged from 27 to 79 years; the mean age was 56.5. The most common clinical complaint was of painful ulcers that failed to resolve within several weeks. Thirty patients had no known history of pemphigus, while in three patients a history of pemphigus was known. The most common clinical impression was that of mucous membrane pemphigoid, but the differential diagnosis included other vesiculoerosive conditions.

Systematic approach to community risk assessment and management.

A move from institutional to community health care means that health service staff are increasingly requested to visit patients in their own homes. This undertaking is not without risk, particularly where the patient or the locality is unknown. There are no nationally available guidelines for formally assessing potential risk to a health worker before the home visit. A protocol for risk assessment and a safety schedule before making a home visit was therefore developed and is described in this article. The difficulties in carrying out a comprehensive risk assessment are outlined. Several ways in which the assessment of risk before home visits could be made more effective are suggested.

Laser peel: facial rejuvenation with a superficial erbium:YAG laser treatment.

BACKGROUND: Facial rejuvenation is a popular procedure to temporarily mask the effects of aging. Most patients desiring this treatment are younger and want improvement without any down time. This study was conducted to evaluate the use of Er:YAG laser as a facial rejuvenation tool. METHODS: The full faces of 18 volunteers were treated with an Er:YAG laser using a fluence of either 5 or 10 J/cm2. All volunteers applied EMLA cream (lidocaine 2.5% and prilocaine 2.5%) two hours before the procedure and were treated with a single pass using a pulse duration of about 300 microseconds. Follow-up visits were made in order to evaluate the degree of discomfort, erythema, swelling and improvement in skin aging. Skin biopsy was performed in one volunteer before and two hours after EMLA application, although preceding laser treatment. RESULTS: Most volunteers experienced moderate discomfort during the treatment. There was mild to moderate erythema and mild swelling. The improvement in general skin appearance, actinic bronzing and photo-damage was mild to moderate. The microscopic evaluation of pre-laser treated skin two hours after EMLA application was suggestive of increased water content in the dermis. CONCLUSION: The Er:YAG laser is an effective and safe tool for facial rejuvenation. With a superficial treatment, resolution of intense erythema is fairly rapid, averaging two to three days. The improvement, however, is mild compared to full laser skin resurfacing (LSR).

Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes.

Stickler and Marshall syndromes are dominantly inherited chondrodysplasias characterized by midfacial hypoplasia, high myopia, and sensorineural-hearing deficit. Since the characteristics of these syndromes overlap, it has been argued whether they are distinct entities or different manifestations of a single syndrome. Several mutations causing Stickler syndrome have been found in the COL2A1 gene, and one mutation causing Stickler syndrome and one causing Marshall syndrome have been detected in the COL11A1 gene. We characterize here the genomic structure of the COL11A1 gene. Screening of patients with Stickler, Stickler-like, or Marshall syndrome pointed to 23 novel mutations. Genotypic-phenotypic comparison revealed an association between the Marshall syndrome phenotype and splicing mutations of 54-bp exons in the C-terminal region of the COL11A1 gene. Null-allele mutations in the COL2A1 gene led to a typical phenotype of Stickler syndrome. Some patients, however, presented with phenotypes of both Marshall and Stickler syndromes.

A novel plant-derived inhibitor of cAMP-mediated fluid and chloride secretion.

We have identified an agent (SP-303) that shows efficacy against in vivo cholera toxin-induced fluid secretion and in vitro cAMP-mediated Cl- secretion. Administration of cholera toxin to adult mice results in an increase in fluid accumulation (FA) in the small intestine (FA ratio = 0.63 vs. 1.86 in control vs. cholera toxin-treated animals, respectively). This elevation in FA induced by cholera toxin was significantly reduced (FA ratio = 0.70) in animals treated with a 100 mg/kg dose of SP-303 at the same time as the cholera treatment. Moreover, when SP-303 was administered 3 h after cholera toxin, a dose-dependent inhibition of FA levels was observed with a half-maximal inhibitory dose of 10 mg/kg. In Ussing chamber studies of Caco-2 or T84 monolayer preparations, SP-303 had a significant effect on both basal current and forskolin-stimulated Cl- current. SP-303 also induced an increase in resistance that paralleled the observed decrease in current. These data suggest that SP-303 has an inhibitory effect on cAMP-mediated Cl- and fluid secretion. Thus SP-303 may prove to be a useful broad-spectrum antidiarrheal agent.

Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa.

Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher syndrome type IIa patients were identified in a gene (USH2A) isolated from this critical region. The USH2A gene encodes a protein with a predicted size of 171.5 kilodaltons that has laminin epidermal growth factor and fibronectin type III motifs; these motifs are most commonly observed in proteins comprising components of the basal lamina and extracellular matrixes and in cell adhesion molecules.

CHARGE association: an update and review for the primary pediatrician.

CHARGE association is a nonrandom pattern of congenital anomalies that occurs together more frequently than one would expect on the basis of chance. This common multiple anomaly condition has an estimated prevalence of 1:10,000. The number of children diagnosed with CHARGE association is increasing, owing presumably to greater awareness of this condition and advances in the care of complex, chronically ill children, resulting in improved survival and outcome. This review of CHARGE association presents diagnostic criteria that may define a concise, recognizable syndrome with a single pathogenetic basis. This review also summarizes our current understanding of the management for this complex and chronic multiple congenital anomaly condition and discusses the pathogenetic basis for this condition.

Deregulated expression and function of CFTR and Cl- secretion after activation of the Ras and Src/PyMT pathways in Caco-2 cells.

We evaluated the role of the activated Ras and Src/PyMT (Polyoma Middle T) signaling pathways on the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in human colonic Caco-2 cell lines. Control vector-transfected Caco-2 cell monolayer preparations (Caco-2-H) responded to forskolin with an increase in short circuit current (Isc) mediated by CFTR. Furthermore, Caco-2-H cells responded to ATP, a reported stimulator of intracellular Ca2+ (Cai2+), and a potential source of adenosine-mediated elevation of cAMP. In contrast, Caco-2 cells transfected with PyMT (Caco-2-MT), expressing high levels of PKC, showed no sustained Isc response to forskolin or ATP. Pretreatment of Caco-2-MT cells with 2.5 microM phorbol 12-myristate 13-acetate (PMA) for 24 hr. effectively down-regulated PKC activity and restored expression of CFTR mRNA but failed to re-establish functional CFTR. These data suggest that, stable up-regulation of PKC alpha, consequent to activation of the Ras or Src/PyMT pathways, leads to an absence of CFTR expression and Cl- secretion mediated by either cAMP or Cai2+. Moreover, Cl- secretion in the colonic Caco-2 epithelial cell line is mediated primarily by CFTR and an alternate Cai(2+)-activated Cl- channel is not functional in these cells.

The novel inotropic agent CGP 48506 alters force primarily by Ca(2+)-independent mechanisms in porcine skinned trabeculae.

OBJECTIVES: The aim was to determine whether, and by what mechanism(s), a novel inotropic agent 5-methyl-6-phenyl-1,3,5,6-tetrahydro-3, 6-methano-1,5-benzodiazocine-2,4-dione (BA 41899) and its enantiomers directly alter the Ca2+ sensitivity of cardiac myofilaments. METHODS: Porcine ventricular trabeculae were permeabilised with Triton X-100. The relationship between force and pCa (-log[Ca2+]) was determined in the presence and absence of ATP. Troponin I was extracted, using vanadate, to produce unregulated maximally activated myofilaments. Force and actomyosin ATPase activity were measured simultaneously to determine tension cost (ATPase activity/tension). The effects of the (+) enantiomer (CGP 48506) on the twitch of intact muscle were demonstrated using rat papillary muscle. RESULTS: 100 microM BA 41899 had a pronounced Ca2+ sensitising effect on force production by porcine skinned cardiac fibres, increasing the pCa required for 50% maximal activation by 0.64 units, while suppressing maximum force by 18.3%. Resting tension was unaffected. These actions were primarily caused by CGP 48506 and were concentration dependent. At concentrations less than 100 microM, CGP 48506 also increased twitch amplitude in intact papillary muscles with no effect on resting tension, whereas 100 microM CGP 48506 increased resting force due to a slowing of relaxation. 100 microM CGP 48506 potentiated Ca(2+)-independent rigor tension in skinned trabeculae, indicating a Ca2+ sensitising mechanism unrelated to Ca2+ binding to troponin C. Tension cost was unaffected by 100 microM CGP 48506 over the entire range of activating Ca2+ concentrations. Suppression of maximum force by CGP 48506 was independent of both Ca2+ concentration and the regulatory troponin complex. CONCLUSIONS: Both the increase in Ca2+ sensitivity during submaximal activation and the depression of maximum force which are induced by CGP 48506 in skinned trabeculae occur at least partly through Ca(2+)-independent mechanisms.

Nitric oxide inhibits depolarization-induced release of endogenous dopamine in the rabbit retina.

The effect of nitric oxide donor compounds (sodium nitroprusside, hydroxylamine and S-nitroso-N-acetyl-D,L-penicillamine) on depolarization-induced release of endogenous dopamine in the light-adapted, isolated retina of the rabbit was studied by HPLC. All three compounds had the same effect, reducing the amount of dopamine released by up to 90%. The effect was concentration dependent, saturating at 300 microM; it was blocked by the nitric oxide scavenger, mannitol (50 mM), which by itself had no effect on the basal release of dopamine. GABAA receptors were not involved. Possible cellular mechanisms underlying the findings are discussed. It is suggested that the inhibitory interaction between dopamine and nitric oxide could represent a higher order function in the light adaptation process in the retina.

Linkage of Usher syndrome type I gene (USH1B) to the long arm of chromosome 11.

Usher syndrome is the most commonly recognized cause of combined visual and hearing loss in technologically developed countries. There are several different types and all are inherited in an autosomal recessive manner. There may be as many as five different genes responsible for at least two closely related phenotypes. The nature of the gene defects is unknown, and positional cloning strategies are being employed to identify the genes. This is a report of the localization of one gene for Usher syndrome type I to chromosome 11q, probably distal to marker D11S527. Another USH1 gene had been previously localized to chromosome 14q, and this second localization establishes the existence of a new and independent locus for Usher syndrome.

Early experience with the gamma interlocking nail for peritrochanteric fractures of the proximal femur.

Surgical fixation, early weight-bearing, and bony union remain a challenge in the treatment of peritrochanteric femur fractures, especially if the fractures are comminuted or unstable. Preliminary experience with the Gamma locking nail, a short intramedullary nail connected to a sliding compression screw augmented with distal locking screws, is presented. In a consecutive series of 29 patients, all fractures were adequately reduced and immediate weight-bearing was begun regardless of fracture configuration (13/27 fractures classified as unstable). Twenty-seven patients were reviewed at 6 months. At follow-up, all patients continued to be ambulatory and all fractures healed. Major complications included screw migration in the femoral head (two patients), difficulty in securely placing the distal screws (eight patients), and a femoral shaft fracture through the distal locking screws following a fall. The technical problems inherent in the device and its instrumentation are discussed. In this early experience, the Gamma nail appears to allow for early patient ambulation regardless of the fracture configuration with excellent clinical results.

Localization of Usher syndrome type II to chromosome 1q.

Usher syndrome is characterized by congenital hearing loss, progressive visual impairment due to retinitis pigmentosa, and variable vestibular problems. The two subtypes of Usher syndrome, types I and II, can be distinguished by the degree of hearing loss and by the presence or absence of vestibular dysfunction. Type I is characterized by a profound hearing loss and totally absent vestibular responses, while type II has a milder hearing loss and normal vestibular function. Fifty-five members of eight type II Usher syndrome families were typed for three DNA markers in the distal region of chromosome 1q: D1S65 (pEKH7.4), REN (pHRnES1.9), and D1S81 (pTHH33). Statistically significant linkage was observed for Usher syndrome type II with a maximum multipoint lod score of 6.37 at the position of the marker THH33, thus localizing the Usher type II (USH2) gene to 1q. Nine families with type I Usher syndrome failed to show linkage to the same three markers. The statistical test for heterogeneity of linkage between Usher syndrome types I and II was highly significant, thus demonstrating that they are due to mutations at different genetic loci.

The child with multiple congenital anomalies.

Specific ways to improve the delivery of comprehensive care to a family whose child has multiple congenital anomalies include the following: 1. Develop a diagnostic plan which establishes medical, psychosocial, and developmental priorities at different ages. 2. Keep lists in the front of the chart which allow easy reference regarding problems, procedures, and resources. 3. Establish communication with designated community and educational coordinators, discussing who will be rendering which services. 4. Ask the parents to keep a notebook which will serve as a repository for notes and communication, accessible to all people caring for the child. Though some of these ideas require extra time at the beginning, the time saved later can be significant.

Design and use of a novel peracetic acid sterilizer for absolute barrier sterility testing chambers.

Increasing use is being made of absolute barrier chambers in the pharmaceutical industry for sterility testing of sterile pharmaceuticals. Since these barriers are designed to form a microbial-tight enclosure to eliminate laboratory microbial contamination derived from the operator and the environment,it is important that the method used to sterilize these barriers, product containers, and articles used within, provide a high degree of sterility assurance. A major part of incorporating absolute barriers in the sterility testing laboratory at the Upjohn Company was to design an automated sterilization system to facilitate the spraying of a liquid sterilant, e.g., peracetic acid, inside these barriers. This article focuses on general design considerations, specific details of the apparatus, and the operational steps. The sterilization efficacy of this method is also described, with particular emphasis on validation criteria and results. Finally, operational sterility testing results are discussed.

Usher syndrome: clinical findings and gene localization studies.

The issue of genetic heterogeneity is a critical problem in the localization of the gene(s) for Usher syndrome. Based on the data obtained on families studied to date, the differences between type I and type II Usher syndrome appear quite distinct with regard to auditory and vestibular function. Although the majority of families can be confidently diagnosed as typical type I or type II, clinical investigations revealed four families with findings that did not fit into either of the two more common subtypes. These findings emphasize the critical importance of an in-depth clinical analysis concomitant with the linkage investigation to assure accurate subtyping of Usher syndrome. Based on an analysis of only those families with definite type I or type II Usher syndrome, approximately 17% of the genome can be excluded as a potential site of the gene for type I, and 14% can be excluded as the site for the type II gene. This study will continue until the Usher gene(s) is successfully localized.