Practical management of patients with non-small-cell lung cancer treated with gefitinib.

PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.     

Human papillomaviruses and small cell carcinoma of the uterine cervix.

The in vitro DNA amplification technique of polymerase chain reaction was used to evaluate the possible presence of human papillomavirus (HPV) in small cell carcinoma of the uterine cervix. None of the 12 cases examined contain detectable amounts of either HPV type 16, 18, 31, or 33 DNA. On the other hand, HPV types 16 and 18 DNA were found in 14 (93.3%) and 9 (60.0%) of 25 invasive cervical squamous carcinoma tissues. The results seem to suggest that these types of HPV are not present or are present in extremely small quantities in cervical small cell carcinoma. Such an absence of HPV DNA makes it unlikely that these types of HPV play any etiological role in the pathogenesis of cervical small cell carcinoma.     

Distribution of, and immune response to, chicken anti-alpha Gal immunoglobulin Y antibodies in wild-type and alpha Gal knockout mice

Chicken antibodies (immunoglobulin Y; IgY) to the alpha Gal epitope (galactose alpha-1,3-galactose) bind to alpha Gal antigens of mouse and porcine tissues and endothelial cells in vitro and block human anti-alpha Gal antibody binding, complement activation and antibody-dependent cell-mediated lysis mechanisms. The activities and toxicity of anti-alpha Gal IgY have not been tested in vivo. In this study, we tested the effects of multiple injections of affinity-purified anti-alpha Gal IgY (AP-IgY) in both wild-type (WT) and alpha-1,3-galactosyltransferase knockout (Gal KO) mice. WT and Gal KO mice were injected once, twice, three, or four times intravenously (i.v.) with AP-IgY and killed at 1 hr or 24 hr. Mice displayed no toxicity to four injections of AP-IgY. Heart, lung, liver, kidney, spleen and pancreatic tissue were evaluated using immunohistochemical techniques for the presence of the alpha Gal epitope using the GSI-B4 lectin, and for bound IgY, as well as mouse IgM and IgG. The binding of AP-IgY antibodies to the endothelium of WT mouse tissues was essentially identical to the pattern of binding of the GSI-B4 lectin after injection of WT mice and death at 1 hr. WT mice killed 24 hr after i.v. injection of AP-IgY showed little remaining bound IgY in their endothelia, indicating that IgY is cleared over that time period. We also evaluated the blood drawn at the time of death for the presence of anti-alpha Gal IgY, anti-IgY IgM and anti-IgY IgG by enzyme-linked immunosorbent assay. Anti-alpha Gal IgY was almost undetectable in WT mouse sera at all injection and killing times. In contrast, Gal KO mouse sera showed increasing anti-alpha Gal IgY levels until 24 hr after the fourth injection, when anti-alpha Gal IgY levels were almost undetectable. Anti-IgY IgM and IgG levels in WT and Gal KO mouse sera showed a typical increase in anti-IgY IgM 24 hr after the second injection (3 days after the first injection) and an increase in anti-IgY IgG 24 hr after the third injection (5 days after the first injection). These results show that IgY binds to alpha Gal epitopes in the WT mice and is cleared sometime over a 24-hr time period and that IgY is an expected immunogen in mice eliciting a rather typical anti-IgY IgM and IgG response.     

Germinal center formation in mice lacking αβ T cells

T cells are essential for inducing clonal B cell expansion in germinal centers during T cell-dependent antibody responses. However, class-switched antibodies are readily detectable in TCRα-deficient mice that congenitally lack αβ T cells, including those such as IgG1 that are considered to be dependent on collaboration between B cells and αβ T cells. This observation suggests that a novel form of B:T collaboration may be evident in TCRα^?/? mice. We report that germinal centers develop spontaneously in mice lacking T cell receptor α genes (TCRα^?/?), despite the absence of αβ T cells. They are not seen in TCRβ^?/? mice kept in similar conditions. Both strains of mice have γδ T cells, but it is a subset of T cells expressing TCRβ and CD4 that is dominant in the germinal centers of TCRα^?/? mice. Exceptionally, germinal centers were associated with CD4⁺ γδ T cells. The expression of CD4 seems to be important, for few extrafollicular T cells have CD4 and CD4 is largely absent from TCRβ^?/? T cells. The CD4⁺ TCRβ cells may help B cells produce autoantibodies that have been identified in TCRα^?/? mice.     

The Effects of Sleep Quality and Resilience on Perceived Stress,Dietary Behaviors,and Alcohol Misuse: A Mediation-Moderation Analysis of Higher Education Students from Asia,Europe, and North America during the COVID-19 Pandemic

Background: The coronavirus disease 2019 (COVID-19) pandemic has increased the already high levels of stress that higher education students experience. Stress influences health behaviors, including those related to dietary behaviors, alcohol, and sleep; yet the effects of stress can be mitigated by resilience. To date, past research studying the connections between dietary behaviors, alcohol misuse, sleep, and resilience commonly investigated singular relationships between two of the constructs. The aim of the current study was to explore the relationships between these constructs in a more holistic manner using mediation and moderation analyses. Methods: Higher education students from China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands, and the United States were enrolled in a cross-sectional study from April to May 2020, which was during the beginning of the COVID-19 pandemic for most participants. An online survey, using validated tools, was distributed to assess perceived stress, dietary behaviors, alcohol misuse, sleep quality and duration, and resilience. Results: 2254 students completed the study. Results indicated that sleep quality mediated the relationship between perceived stress and dietary behaviors as well as the relationship between perceived stress and alcohol misuse. Further, increased resilience reduced the strength of the relationship between perceived stress and dietary behaviors but not alcohol misuse. Conclusion: Based on these results, higher education students are likely to benefit from sleep education and resilience training, especially during stressful events.     

Idiopathic arterial calcification of infancy: sonographic and magnetic resonance findings with pathologic correlation

Idiopathic arterial calcification of infancy is a rare condition characterized by extensive arterial calcification and stenoses of large and medium sized arteries. We report the sonographic and magnetic resonance angiographic findings of this entity and correlate them with the findings at autopsy. Received: 20 October 1997 Accepted: 21 November 1997     

Avulsion fracture of the base of the fifth metatarsal not seen on conventional radiography of the foot: the need for an additional projection

OBJECTIVE: To our knowledge, this article is the first to describe a series of patients with avulsion fractures of the base of the fifth metatarsal that were not seen on conventional radiography using the standard three views of the foot but that were seen on radiography of the ankle. CONCLUSION: Because routine radiographs of the foot may fail to reveal an avulsion fracture of the base of the fifth metatarsal, an additional projection should be obtained to better assess this region in the symptomatic patient. The additional view should be an anteroposterior radiograph of the ankle that includes the base of the fifth metatarsal because this projection has been shown to help in the diagnosis of this avulsion fracture.     

Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals

Many HIV-infected individuals on antiretroviral therapy (ART) exhibit persistent systemic inflammation, which predicts morbidity and mortality. ART-treated subjects concurrently exhibit marked compositional alterations in the gut bacterial microbiota and the degree of dysbiosis correlates with systemic inflammation. Whether interventions to modulate the microbiome can affect systemic inflammation is unknown. An open-label fecal microbial transplantation (FMT) was delivered by colonoscopy to asymptomatic HIV-infected ART-suppressed individuals without antibiotic pre-treatment. Stool was assessed before and after FMT for engraftment of donor microbes, and peripheral blood was assayed for immune activation biomarkers. Six participants received FMT and 2 participants served as controls. No serious adverse effects occurred during 24 weeks of follow-up. At baseline, HIV-infected individuals exhibited microbiota profiles distinct from uninfected donors. During the 8 weeks post-FMT, recipients demonstrated partial engraftment of the donor microbiome (P < 0.05). Recipient microbiota remained significantly distant from donors, unlike that observed following FMT for treatment of C. difficile infection. Systemic inflammatory markers showed no significant change post-FMT. FMT was well-tolerated in ART-treated, HIV-infected individuals. Engraftment was detectable but modest, and appeared to be limited to specific bacterial taxa. Whether antibiotic conditioning can enhance engraftment and the capacity of microbiota to modulate inflammation remains to be investigated.     

Effects of Crede's method on urine voiding within the first 8 h after surgery among post‐haemorrhoidectomy patients: a comparison study

Urinary retention is a common complication among patients after haemorrhoidectomy. Although Crede's method is recommended for urinary retention in nursing practice textbooks, its effects require further examination. The purpose of this study was to investigate the rate of urine voiding within the first 8 h following haemorrhoidectomy and to examine the effects of Crede's method on this postoperative outcome. A two‐group comparison study was conducted. All participants were over 20 years of age, and each had undergone haemorrhoidectomy. Outcome measurements included patients' self‐reported urine voiding within 8 h of surgery, personal demographics and disease‐related data. Before the surgical procedure, participants were divided into Crede's group and non‐Crede's group, and written educational materials were given. Patients in the Crede's group were taught Crede's method for application in the event that they were unable to void urine after haemorrhoidectomy. The non‐Crede's group patients were taught traditional methods without Crede's method. We examined urine voiding within the first 8 h after haemorrhoidectomy. The mean rate of urine voiding within 8 h of surgery was 60·9% overall, with 91·3% (21/23) in the Crede's group and 30·4% (7/23) in the non‐Crede's group reporting successful voiding. After controlling for the two groups' personal characteristics and disease‐related variables, age, educational level and perioperative fluid administration were treated as covariates and included in the multinomial logistic regression model. The odds ratio of urine voiding within the first 8 h after surgery was 52·70‐fold higher in the Crede's group than in the non‐Crede's group (p < 0·01). This study shows that Crede's method is an effective strategy to aid in urine voiding within the first eight postsurgical hours among patients following haemorrhoidectomy. Clear and concise information about urinary retention and related management strategies should be given to patients before haemorrhoidectomy.