Atopic dermatitis: clinical relevance of food hypersensitivity reactions

Forty-six patients with atopic dermatitis ranging from mild to severe were evaluated for food hypersensitivity with double-blind placebo-controlled food challenges. Twenty-eight (61%) patients had a positive prick skin reaction to one of the foods tested. Sixty-five food challenges were performed; 27 (42%) were interpreted as positive in 15 (33%) patients. Egg, milk, and peanut accounted for 78% of the positive reactions. As in previous studies, patients developed skin (96%), respiratory (52%), or gastrointestinal (30%) symptoms during the challenge. These studies indicate that children who have atopic dermatitis unresponsive to routine therapy or who continue to need daily treatment after several months would benefit from evaluation for food hypersensitivity.     

The influence of children's self-report trait anxiety and depression on visual search for emotional faces

BACKGROUND: This study presents two experiments that investigated the relationship between 7- and 10-year-olds' levels of self-report trait anxiety and depression and their visual search for threatening (angry faces) and non-threatening (happy and neutral faces) stimuli. METHOD: In both experiments a visual search paradigm was used to measure participants' reaction times to detect the presence or absence of angry, happy or neutral schematic faces (Experiment 1) or cartoon drawings (Experiment 2). On target present trials, a target face was displayed alongside three, five or seven distractor items. On target absent trials all items were distractors. RESULTS: Both experiments demonstrated that on target absent (but not present) trials, increased levels of anxiety produced significantly faster search times in the angry face condition, but not in the neutral condition. In Experiment 2 there was some trend towards significance between anxiety and searches for happy faces in absent trials. There were no effects of depression on search times in any condition. CONCLUSION: The results support previous work highlighting a specific link between anxiety and attention to threat in childhood.     

Variable Genomic Landscapes of Advanced Melanomas with Heavy Pigmentation

BackgroundIn the current study, we examined the real-world prevalence of highly pigmented advanced melanomas (HPMel) and the clinicopathologic, genomic, and ICPI biomarker signatures of this class of tumors.Materials and MethodsOur case archive of clinical melanoma samples for which the ordering physician requested testing for both PD-L1 immunohistochemistry (IHC) and comprehensive genomic profiling (CGP) was screened for HPMel cases, as well as for non-pigmented or lightly pigmented advanced melanoma cases (LPMel).ResultsOf the 1268 consecutive melanoma biopsies in our archive that had been submitted for PD-L1 IHC, 13.0% (165/1268) were HPMel and 87.0% (1103/1268) were LPMel. In the HPMel cohort, we saw a significantly lower tumor mutational burden (TMB, median 8.8 mutations/Mb) than in the LPMel group (11.4 mut/Mb), although there was substantial overlap. In examining characteristic secondary genomic alterations (GA), we found that the frequencies of GA in TERTp, CDKN2A, TP53, and PTEN were significantly lower in the HPMel cases than in LPMel. A higher rate of GA in CTNNB1, APC, PRKAR1A, and KIT was identified in the HPMel cohort compared with LPMel.ConclusionsIn this study, we quantified the failure rates of melanoma samples for PD-L1 testing due to high melanin pigmentation and showed that CGP can be used in these patients to identify biomarkers that can guide treatment decisions for HPMel patients. Using this practical clinical definition for tumor pigmentation, our results indicate that HPMel are frequent at 13% of melanoma samples, and in general appear molecularly less developed, with a lower TMB and less frequent secondary GA of melanoma progression.     

The MDR1 (P-glycoprotein) and MRP (P-190) transporters do not play a major role in the intrinsic multiple drug resistance of Jurkat T lymphocytes

The response of T cells in relation to the cell cycle has not been extensively studied. We have attempted to address this question using Jurkat T cells treated with cytostatic drugs known to arrest cells at various transition points of their cycle. We tested several concentrations of drugs that act at G1/S (hydroxyurea, lovastatin, thymidine), early S (aphidicolin, cyclosporin A, rapamycin) or G2+M (colchicine, nocodazole) in 24 h cultures. Cytofluorimetric analyses showed that cycling Jurkat cells were equally distributed between the G1 (44.9 ± 6.5%) and S (42.3 ± 8.0%) phases. Cell distribution in G2+M was 12.7 ± 2.8%. Hydroxyurea but not lovastatin increased the percentage of cells in S phase to ≈60–70% and both drugs decreased it to ≈30% in G1. Thymidine had no effects. Aphidicolin increased the distribution in S phase to ≈70% with a decrease in G1 to ≈30%. Cyclosporin A and rapamycin increased the percentage of the cells in G1 to ≈70% and decreased it to ≈25% in S phase. Nocodazole increased cell distribution in G2+M to ≈60% and induced a decrease in G1 to ≈10%. The effects of the drugs were not related to their toxicity and their limited efficiency raised the possibility that Jurkat cells possessed an intrinsic resistance to these xenobiotics. Time-course analysis showed (scanning electron microscopy) that the early morphological changes induced by colchicine were reversible. Drug efflux experiments (vinblastine) suggested that an ATP-dependent process could be involved. However, Northern blot analyses showed a weak signal for MDR1 (P-glycoprotein). In contrast, a probe for MRP (P-190) showed a strong signal in Jurkat and peripheral lymphocytes. The presence of drugs (cyclosporin A, nocodazole, thymidine) (24 h) did not upregulate its message and cell treatment with -butathione (S,R)-sulfoximine only moderately affected the efficiency of the glutathione S-conjugate MRP transporter. Our data suggest that the intrinsic multidrug resistance of leukemic Jurkat T cells does not appear to involve the MDR1 and MRP members of the ABC family of reverse drug transporters and these observations raise the possibility of the involvement of multifaceted mechanisms.     

Exposure to power frequency electric fields and the risk of childhood cancer in the UK

The United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of Great Britain, incorporated a pilot study measuring electric fields. Measurements were made in the homes of 473 children who were diagnosed with a malignant neoplasm between 1992 and 1996 and who were aged 0-14 at diagnosis, together with 453 controls matched on age, sex and geographical location. Exposure assessments comprised resultant spot measurements in the child's bedroom and the family living-room. Temporal stability of bedroom fields was investigated through continuous logging of the 48-h vertical component at the child's bedside supported by repeat spot measurements. The principal exposure metric used was the mean of the pillow and bed centre measurements. For the 273 cases and 276 controls with fully validated measures, comparing those with a measured electric field exposure >/=20 V m(-1) to those in a reference category of exposure <10 V m(-1), odds ratios of 1.31 (95% confidence interval 0.68-2.54) for acute lymphoblastic leukaemia, 1.32 (95% confidence interval 0.73-2.39) for total leukaemia, 2.12 (95% confidence interval 0.78-5.78) for central nervous system cancers and 1.26 (95% confidence interval 0.77-2.07) for all malignancies were obtained. When considering the 426 cases and 419 controls with no invalid measures, the corresponding odds ratios were 0.86 (95% confidence interval 0.49-1.51) for acute lymphoblastic leukaemia, 0.93 (95% confidence interval 0.56-1.54) for total leukaemia, 1.43 (95% confidence interval 0.68-3.02) for central nervous system cancers and 0.90 (95% confidence interval 0.59-1.35) for all malignancies. With exposure modelled as a continuous variable, odds ratios for an increase in the principal metric of 10 V m(-1) were close to unity for all disease categories, never differing significantly from one.     

A change in treatment process with a modern record and verify system

Purpose: With the introduction of new treatment devices, such as a multileaf collimator (MLC) and dynamic wedge (DW), therapists have an increased responsibility to ensure correct treatment. Simultaneously, three-dimensional treatment planning (3DTP) has led to an increased number of portals and table movements. To counteract this challenge and maintain efficiency, a comprehensive record and verify (R&V) system is mandatory. We evaluated a commercial system (Varis) for reliability, ease of use, efficiency, and integration with our planning systems.

Methods and Materials: Some key elements of the Varis system are: integration of MLC and DW; auto setup for MLC, jaw, collimator, gantry, and limited table parameters; direct download of simulation beam data; and a regimented field scheduling system that prescribes all beam data for particular fractions. Evaluation of the system was driven by treatment time analysis, error rates, and an increased workload. These issues were governed by how we disseminated duties and how the system accommodated or changed our processes.

Results: Most data entry is performed by our dosimetry staff. Data can be downloaded from the simulator, but more patients now move from CT simulation and/or 3DTP to the treatment machine. Varis does not link to these systems. The physics staff confirms all entries to correct data entry errors. The workload for dosimetrists increased by an average of 8 minutes/patient entry; physics time increased by 7 minutes/patient entry; the weekly electronic chart check takes approximately 3 minutes/patient. Therapists who used Varis efficiently showed a slight decrease in treatment times, attributed to MLC integration and auto-setup. Some therapists experienced a decrease in efficiency, because of unfamiliarity and excess intervention. On a positive note, notable events have decreased by a factor of 10 since full initiation. Unfortunately, the remaining errors are often the result of a therapist relying on incorrect electronic information.

Conclusion: The Varis R&V system has had an impact on our clinic’s process and efficiency. Checking of all beam data and related field scheduling have helped reduce errors and misconceptions. We feel a dual-energy machine can be operated with two experienced therapists and an up-to-date R&V system more accurately and efficiently than with three therapists working without an integrated R&V. We anticipate future Varis releases will further promote efficiency and accuracy.     

Perinatal transmission of Trichomonas vaginalis: a case report

BACKGROUND: Trichomonas vaginalis infection is associated with increased risks of adverse pregnancy outcome. Perinatal transmission of T vaginalis from an infected, untreated, pregnant woman to her female neonate can occur. CASE: A 22-year-old woman, gravida 3, para 2, with untreated trichomoniasis had an uncomplicated spontaneous vaginal delivery of a healthy female infant. At day of life 19 the newborn was diagnosed and treated for trichomoniasis. No evidence was found consistent with child sexual abuse. CONCLUSION: Perinatal transmission of T vaginalis occurs rarely. Neonatal infection has medical and psychosocial implications. This outcome, albeit rare, should be a consideration in the decision regarding antenatal treatment of T vaginalis infection.     

Hormonal contraception and HIV-positive women: metabolic concerns and management strategies

As HIV-positive women live longer lives, and as testing for HIV becomes more routine, clinicians can expect to see more HIV-positive women in their practices. The need to be aware of management issues particular to this population becomes increasingly important. Metabolic dysregulation is a common, long-term complication associated with HIV and is one of the most difficult to manage. Hormonal contraception also is associated with metabolic dysregulation. As more HIV-positive women choose long-term, reversible contraception, the potential for concomitant and additive side effects, and the need for careful, proactive management strategies to avoid these complications, will become more important. This article reviews research detailing the metabolic dysfunction associated with hormonal contraception and with HIV-seropositivity. It highlights reasons for concern regarding the potential, although as yet theoretical, increased risk for metabolic dysfunction when hormonal contraception is used in the presence of HIV. Suggestions for management strategies for women living with HIV who choose to use hormonal contraception are presented. These strategies should be viewed as suggestions for management until substantitive research becomes available.