Comparison of cost changes due to the COVID-19 pandemic for Dermatology residency applications in the USA.

We performed a cost estimation of dermatology residency applications prior to COVID-19 pandemic restrictions (2016-2020) and during the COVID-19 pandemic (2021) and surveyed dermatology programme directors to assess the impact of virtual interviews. We found that COVID-19 virtual interviews significantly reduced the cost of applications. We understand that the changes forced by the pandemic were challenging and not ideal; however, the online aspect of interviews provided a way for applicants to save a significant amount of money.

Gentian violet for pyoderma gangrenosum: a retrospective chart review.

Pyoderma gangrenosum is a rare autoinflammatory skin disease. Treatment is multifactorial, addressing inflammation, pain, underlying disease, if present, and the wound. Gentian violet has been used for hundreds of years in a variety of dermatologic conditions for its anti-inflammatory properties. This study aims to evaluate gentian violet in wound healing for pyoderma gangrenosum. We conducted a retrospective chart review of patients with pyoderma gangrenosum treated with gentian violet at the Wake Forest School of Medicine Department of Dermatology in the last 10 years. The primary outcome was clinical improvement. Of the 34 cases that met inclusion criteria, 70% improved with gentian violet, 24% had no documented change, 3% initially improved then worsened, and 3% had unclear results. Gentian violet is a safe and cheap treatment that may improve resolution of pyoderma gangrenosum lesions in addition to systemic therapy.

Does daily folic acid supplementation reduce methotrexate efficacy?

Methotrexate is a mainstay treatment for autoimmune and inflammatory conditions in the field of Dermatology. However, in some patients, its use is associated with significant side effects and toxicity. Folate supplementation with either folic acid or folinic acid often mitigates side effects and reduces the incidence of systemic toxicity related to methotrexate. Although the value of methotrexate is clear, debate remains about folate supplementation. There is little agreement about the proper dosing or frequency of folate supplementation as many believe that daily folate supplementation can reduce methotrexate efficacy. Although daily use of folic acid does not appear to affect methotrexate efficacy, dosing of folinic acid close to methotrexate administration may hinder methotrexate efficacy. Therefore, folic acid should be used daily with methotrexate to ameliorate side effects, whereas folinic acid should only be used for methotrexate toxicity.

Abnormal liver function tests in acne patients receiving isotretinoin.

BACKGROUND: Isotretinoin is an efficacious treatment option for severe acne. Although isotretinoin often causes mild liver enzyme elevation, how acne patients should be monitored on isotretinoin therapy is not well characterized. OBJECTIVE: The purpose of this study was to assess the management and clinical outcome of acne patients with abnormal aspartate transaminase (AST) and alanine aminotransferase (ALT) when receiving isotretinoin. METHODS: A retrospective chart review was conducted in acne subjects with abnormal AST and ALT levels receiving isotretinoin. Abnormal liver enzymes were graded using the Common Terminology Criteria for Adverse Events version 5. RESULTS: Of 108 subjects with abnormal liver enzymes, 79 subjects were on isotretinoin 80 mg and 23 subjects were on isotretinoin 40 mg. Most abnormalities were during Month 1 of therapy (48). Of the 122 abnormal Grade 1 AST elevations, 40 normalized, 38 remained in Grade 1, and 1 increased into Grade 2 when a healthcare provider maintained the isotretinoin dose. Of the 102 abnormal Grade 1 ALT levels managed by maintaining the isotretinoin dose, 31 normalized and 38 remained persistently elevated. CONCLUSION: Most mild elevations of isotretinoin therapy do not worsen. Acne patients with isotretinoin may not need continued testing when experiencing low-grade liver enzyme abnormalities.

Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR1.

Experiments were performed to determine if retroviral-mediated transfer of the human multidrug resistance 1 gene (MDR1) into murine bone marrow cells would confer drug resistance to the cells and whether the MDR1 gene could be used as a dominant selectable marker in vivo. When mice transplanted with bone marrow cells containing a transferred MDR1 gene were treated with the cytotoxic drug taxol, a substantial enrichment for transduced bone marrow cells was observed. This demonstration of positive selection establishes the ability to amplify clones of transduced hematopoietic cells in vivo and suggests possible applications in human therapy.

Substitution of the human beta-spectrin promoter for the human agamma-globin promoter prevents silencing of a linked human beta-globin gene in transgenic mice.

During development, changes occur in both the sites of erythropoiesis and the globin genes expressed at each developmental stage. Previous work has shown that high-level expression of human beta-like globin genes in transgenic mice requires the presence of the locus control region (LCR). Models of hemoglobin switching propose that the LCR and/or stage-specific elements interact with globin gene sequences to activate specific genes in erythroid cells. To test these models, we generated transgenic mice which contain the human Agamma-globin gene linked to a 576-bp fragment containing the human beta-spectrin promoter. In these mice, the beta-spectrin Agamma-globin (betasp/Agamma) transgene was expressed at high levels in erythroid cells throughout development. Transgenic mice containing a 40-kb cosmid construct with the micro-LCR, betasp/Agamma-, psibeta-, delta-, and beta-globin genes showed no developmental switching and expressed both human gamma- and beta-globin mRNAs in erythroid cells throughout development. Mice containing control cosmids with the Agamma-globin gene promoter showed developmental switching and expressed Agamma-globin mRNA in yolk sac and fetal liver erythroid cells and beta-globin mRNA in fetal liver and adult erythroid cells. Our results suggest that replacement of the gamma-globin promoter with the beta-spectrin promoter allows the expression of the beta-globin gene. We conclude that the gamma-globin promoter is necessary and sufficient to suppress the expression of the beta-globin gene in yolk sac erythroid cells.

Cumulative dose-response study of non-CFC propellant HFA 134a salbutamol sulfate metered-dose inhaler in patients with asthma.

STUDY OBJECTIVE: This study compares the safety and efficacy of HFA 134a salbutamol sulfate (Airomir in the 3M CFC-free system [3M Pharmaceuticals]) and CFC 11/12 salbutamol (Ventolin [Allen & Hanburys]) in a cumulative dose-response (1, 1, 2, 4, 8 inhalations at 30-min intervals) study in asthmatic patients. DESIGN: Randomized, single-blind, two-period cross-over study. PARTICIPANTS: Twenty-four stable mild to moderate asthmatics. MEASUREMENTS AND RESULTS: At all cumulative inhalations, the changes in FEV1 (absolute, percent, and percent predicted) and FVC were equivalent. There was also no significant difference in heart rate, serum potassium level, BP, 12-lead ECG, Holter monitor recordings, or adverse events. Both HFA 134a salbutamol sulfate and CFC 11/12 salbutamol displayed a significant dose-response for FEV1, FEF25-75%, FVC, serum potassium, heart rate, and systolic BP. CONCLUSIONS: HFA 134a salbutamol sulfate and CFC 11/12 salbutamol produced clinically and statistically similar airway responses and side effects. These results indicate that HFA 134a salbutamol sulfate would be a safe and effective substitute for CFC 11/12 salbutamol.

Isolation of stem cell-specific cDNAs from hematopoietic stem cell populations.

We have begun to isolate gene sequences that are specifically expressed in hematopoietic stem cells (HSCs). There are at least three fundamental requirements for the isolation of HSC-specific transcripts. First, highly enriched populations of HSCs, and an HSC-depleted cell population for comparison must be isolated. Secondly, the gene isolation procedures must be adapted to accommodate the small amounts of RNA obtained from purified HSCs. Finally, a defined screening strategy must be developed to focus on sequences to be examined in more detail. In this report, we describe the characterization of populations of HSCs that are highly enriched (Lin- c-kitHI) or depleted (Lin- c-kitNEG) of HSCs. We compared two methods for gene isolation, differential display polymerase chain reaction (DD-PCR) and subtractive hybridization (SH), and found that the latter was more powerful and efficient in our hands. Lastly we describe the strategy that we have developed to screen clones for further study.

Improved amphotropic retrovirus-mediated gene transfer into hematopoietic stem cells.

The efficiency of amphotropic retrovirus-mediated gene transfer into human Hematopoietic Stem Cells (HSC) is less than 1%. This has impeded gene therapy for hematopoietic diseases. In this study we demonstrate that populations of mouse and human HSC contain low to undetectable levels of the amphotropic virus receptor mRNA (ampho R mRNA), and are resistant to transduction with amphotropic retroviral vectors. In a subpopulation of mouse HSC expressing 7-fold higher levels of ampho R mRNA, transduction with amphotropic retrovirus vectors was 30-fold higher. We conclude that retrovirus transduction of HSC correlates with ampho R mRNA levels. Our results predict that alternative sources of HSC or retroviruses will be required for human gene therapy of hematopoietic diseases. One alternative source of stem cells is from individuals treated with cytokines. We have previously shown that mice treated with G-CSF and SCF have an immediate increase in peripheral blood HSC immediately after treatment, followed by a 10-fold increase in bone marrow HSC 14 days after treatment. In this report we show that when rhesus monkey bone marrow cells collected 14 days after G-CSF and SCF treatment were transduced with amphotropic retroviruses, gene transfer levels were approximately 10%, which was easily detected by Southern blot analysis. We conclude that the increased gene transfer may be the result of increased expression of the amphotropic retrovirus receptor, increased numbers of cycling HSC or both.

Development of a stable retrovirus vector capable of long-term expression of gamma-globin mRNA in mouse erythrocytes.

Gene therapy for patients with hemoglobin disorders such has been hampered by the inability of retrovirus vectors to transfer globin genes and the locus control region (LCR) into hematopoietic stem cells without rearrangement. In addition, the expression from intact globin gene vectors has been variable in red blood cells as a result of position effects and retrovirus silencing. We hypothesized that by substituting the globin gene promoter for the promoter of another gene expressed in red blood cells, we could generate stable retrovirus vectors that would express globin at sufficient levels to treat hemoglobinopathies. Transgenic mice containing the human ankyrin (Ank) gene promoter fused to the human gamma-globin gene showed position-independent, copy number-dependent expression of a linked gamma-globin mRNA. We generated a "double-copy" Ank/A gamma-globin retrovirus vector that transferred two copies of the Ank/A gamma-globin gene into target cells. Stable gene transfer was observed in primary primary mouse progenitor cells and long-term repopulating hematopoietic stem cells. Expression of Ank/A gamma-globin mRNA in mature red blood cells was approximately 8% of the level of mouse alpha-globin mRNA. We conclude that this novel retrovirus vector may be valuable for treating a variety of hemoglobinopathies by gene therapy if the level of expression can be further increased.

Diabetes insipidus following obstetric shock.

The first known case of obstetric shock followed by diabetes insipidus without anterior pituitary deficiency is presented. A patient developed extreme thirst and polyuria after massive bleeding and prolonged shock due to placenta previa percreta with bladder invasion. Evaluation confirmed diabetes insipidus sensitive to vasopressin administration. Anterior pituitary deficiency could not be identified, either acutely or 6 months later.

Pressure control inverse ratio ventilation in the treatment of adult respiratory distress syndrome in patients with blunt chest trauma.

The objective of this study was to evaluate the efficacy of pressure control inverse ratio ventilation (PCIRV) in improving oxygenation in trauma patients with adult respiratory distress syndrome (ARDS) and to assess the potential risks associated with this form of treatment. This was a cohort study assessing the trends in hemodynamic and ventilatory parameters after the initiation of PCIRV, conducted at a community Level I trauma center intensive care unit. The study comprised 15 trauma patients developing severe, progressive ARDS [two or more of the following criteria: positive end-expiratory pressure (PEEP) >10 cm H2O; arterial partial pressure of oxygen divided by fraction of inspired oxygen (PaO2:FiO2) ratio <150; and peak inspiratory pressure (PIP) >45 cm H2O]: ten due to blunt chest injuries, three due to sepsis, and two due to fat emboli syndrome. PCIRV was initiated. Main outcome measures were PIP, PEEP (total, auto), oxygen saturation, cardiac index, oxygen delivery, PaO2:FiO2 ratio, compliance, evidence of complications of PCIRV, and mortality. Within 24 hours of conversion to PCIRV, the patients stabilized and the mean PaO2:FiO2 ratio rose from 96.3+/-57.8 to 146.8+/-91.1 (P<0.05) and PIP fell from 47.9+/-13.8 to 38.8+/-8.4 cm H2O; auto-PEEP increased from 0.5+/-1.9 to 7.5+/-5.6 cm H2O (P<0.05); oxygen delivery index remained stable (563+/-152 to 497+/-175 mL/min/m2); three patients developed evidence of barotrauma, one patient developed critical illness polyneuropathy, and two patients died (13%). PCIRV is an effective salvage mode of ventilation in patients with severe ARDS, but it is not without complications. Auto-PEEP levels and cardiac index should be monitored to ensure tissue oxygen delivery is maintained.

Pharmacokinetic differences between chlorofluorocarbon and chlorofluorocarbon-free metered dose inhalers of beclomethasone dipropionate in adult asthmatics.

We have compared the serum pharmacokinetics of the metabolites of beclomethasone dipropionate after inhalation from chlorofluorocarbon (CFC) and hydrofluoroalkane HFA-134a (HFA) formulations in asthmatic patients. Twenty-three patients completed this open-label, randomized, single-dose, three-period crossover study. Each patient received in separate periods 200 microg or 400 microg HFA-beclomethasone dipropionate, or 400 microg CFC-beclomethasone dipropionate. Venous blood samples were collected over 24 h for the determination of beclomethasone esters and beclomethasone in the serum. Significant differences in pharmacokinetics following HFA- and CFC-beclomethasone dipropionate were observed. Following a 400 microg beclomethasone dipropionate dose, the HFA formulation gave mean maximum concentrations (Cmax) and area under the curve (AUC) values of beclomethasone esters of 1153 pg mL(-1) and 4328 pg h mL(-1), respectively, and beclomethasone Cmax and AUC values of 69 pg mL(-1) and 682 pg h mL(-1), respectively. These values were approximately 2-3-fold those seen with the CFC formulation (beclomethasone esters Cmax and AUC of 380 pg mL(-1) and 1764 pg h mL(-1), respectively; beclomethasone Cmax and AUC of 41 pg ml(-1) and 366 pg h mL(-1), respectively). Beclomethasone esters, the major component of beclomethasone dipropionate in the serum, peaked significantly earlier for the HFA formulation (0.8 h) than for the CFC formulation (2 h). Tests for dose proportionality of beclomethasone esters pharmacokinetics following HFA-beclomethasone dipropionate showed that the two hydrofluoroalkane strengths were proportional. The more rapid and greater efficiency of systemic drug delivery of the HFA formulation compared with the CFC formulation can be explained if most of each inhalation from CFC-beclomethasone dipropionate is swallowed and absorbed orally, whereas most of each inhalation from HFA-beclomethasone dipropionate is absorbed through the lungs. There is a need for comprehensive dose-response efficacy trials, with the use of the steep portion of the dose-response relationship, to evaluate the significance of these pharmacokinetic differences.

Influence of a carbohydrate drink on nutritional status, body composition and mood during desert training.

BACKGROUND: Nutritional intake by military personnel is typically inadequate during field exercises, potentially compromising health and performance. HYPOTHESIS: Drinking a supplemental carbohydrate (CHO) beverage will increase total caloric intake and maintain nutritional status during military training in the desert. METHODS: A total of 63 volunteers were randomly assigned to one of two groups to receive either a CHO or placebo beverage with military rations during an 11-d desert field exercise. Fluid intake was ad libitum and adequate rations were provided. Blood samples were collected twice to assess nutritional status, and nutrient intake was determined with consumption data. Mood state was examined by questionnaire. RESULTS: Energy intake was significantly higher in the CHO group (3050 kcal x d(-1) vs. 2631 kcal x d(-1)), with additional CHO from the beverage providing energy with some compensation by reduced fat and protein intake. Intakes of energy, folacin, calcium, magnesium, iron, and zinc in both groups were inadequate, with intakes significantly lower (p<0.05) for calcium, magnesium, and zinc in the CHO beverage group. Blood parameters of nutritional status remained within normal ranges with no differences between groups, but significant decreases were seen in pre-albumin. No changes in mood were seen during the training, nor after exposure to desert conditions. CONCLUSIONS: The operational ration supplemented with a CHO beverage significantly increases CHO and energy intakes compared with standard rations and maintains nutritional status for short exercises. Fortification with micronutrients most at risk for deficient intake from foods may be needed for longer deployments.

Fruit and vegetables in the service member's diet: data from military institutional feeding studies.

Previous surveys of the U.S. population have indicated that typical intakes of fruits and vegetables are substantially below recommended levels. Using data from nine dietary studies, we examined 798 service members who subsisted in government-run feeding programs to determine how they differ from the general population. The findings of this retrospective investigation showed that an estimated 43% of service members met the minimum recommendation of five daily servings of fruit and vegetables compared with 6% of the general population. Among genders, more males had fruits and vegetables rich in carotenoids (22 vs. 10%), whereas a slightly higher proportion of females consumed cruciferous vegetables (14 vs. 11%). Only 3% consumed no servings of vegetables, and 11% consumed no servings of fruits. Intake in overall quantity of fruits and vegetables was higher among service members, but further efforts are needed to increase consumption of cruciferous vegetables and fruits and vegetables rich in carotenoids.

Incorporating new recipes into the Armed Forces Recipe File: determination of acceptability.

As part of a project of decrease fat, cholesterol, and sodium in soldiers' diets, new ethnic and breakfast items were developed and standardized for 100 portions. Acceptability data were collected after initial recipe development, during recipe validation at a collaborating university, and in an actual Army garrison. Acceptability was determined using a nine-point hedonic scale; products rating > or = 6.0 in initial tests were prepared in garrison. Acceptability data were compared among test settings, ethnic categories, and food type. When grouped by ethnic categories, acceptability ratings varied more than when grouped by food type. Ratings varied most between development and validation settings (7.2 vs. 6.6; p < 0.05) and least between validation and actual Army settings (6.6 vs. 6.6; not significant). Because acceptability ratings were similar between the validation site and the Army garrison, future recipe development may continue without additional testing at actual Army garrisons, leading to more timely armed forces recipe file additions.