Recombinant HA-based vaccine outperforms split and subunit vaccines in elicitation of influenza-specific CD4 T cells and CD4 T cell-dependent antibody responses in humans.

Although traditional egg-based inactivated influenza vaccines can protect against infection, there have been significant efforts to develop improved formats to overcome disadvantages of this platform. Here, we have assessed human CD4 T cell responses to a traditional egg-based influenza vaccine with recently available cell-derived vaccines and recombinant baculovirus-derived vaccines. Adults were administered either egg-derived Fluzone®, mammalian cell-derived Flucelvax® or recombinant HA (Flublok®). CD4 T cell responses to each HA protein were assessed by cytokine EliSpot and intracellular staining assays. The specificity and magnitude of antibody responses were quantified by ELISA and HAI assays. By all criteria, Flublok vaccine exhibited superior performance in eliciting both CD4 T cell responses and HA-specific antibody responses, whether measured by mean response magnitude or percent of responders. Although the mechanism(s) underlying this advantage is not yet clear, it is likely that both qualitative and quantitative features of the vaccines impact the response.

Population-based analysis of treatment modalities and survival for clinically localized small-cell carcinoma of the prostate.

BACKGROUND: Small-cell carcinoma of the prostate is an aggressive cancer whose rarity has prevented the development of a consensus management approach. The objective of the current study was to determine the treatment patterns and evaluate factors affecting overall survival for patients with localized small-cell carcinoma of the prostate. METHODS: After querying the National Cancer Database, we identified all patients diagnosed with localized small-cell carcinoma of the prostate between 1998 and 2011 (n=287). Using Kaplan-Meier curves and Cox regression analyses, we assessed the effect of treatment and clinical stage on overall survival. RESULTS: Treatments included radiation therapy in 46% (n=131), chemotherapy in 38% (n=107), androgen deprivation therapy (ADT) in 22% (n=63) and radical prostatectomy in 13% (n=38). Median overall survival was 14.8 months. Upon multivariate analysis, local therapy (radical prostatectomy or radiation therapy) was associated with improved survival (hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.14-0.38, P<0.001). Advanced clinical stage predicted worse survival among all men (cT3: HR 2.83, 95% CI 1.27-6.32, P=0.011; cT4: HR 3.26, 95% CI 1.50-7.07, P=0.003) and men who received local therapy (cT3: HR 4.67, 95% CI 1.41-15.44, P=0.012; cT4: HR 4.01, 95% CI 1.14-14.08, P=0.03) but not among men who received no local therapy (cT3: HR 1.64, 95% CI 0.51-5.27, P=0.4; cT4: HR 2.35, 95% CI 0.74-7.48, P=0.15). Age, receipt of chemotherapy and ADT, and clinical stage T2 disease (compared with T1) did not predict survival. CONCLUSION: Men with localized small-cell carcinoma of the prostate have a poor overall survival. Local therapy may represent a suitable and underused modality for select patients.

A novel KIT mutation results in piebaldism with progressive depigmentation.

Piebaldism is an autosomal dominant disorder of melanocyte development characterized by white skin (leukoderma) and white hair (poliosis). In general, piebaldism has been distinguished from vitiligo by the presence of lesions from birth, the hyperpigmented macules of depigmented and normal skin, and the static course. We hypothesized that an 8-year-old girl and her mother who had unusual piebaldism of a progressive nature would have a novel mutation of the KIT gene, the gene that is altered in patients with piebaldism, or of the MITF (microphthalmia activating transcription factor) gene, which would be expected to cause type II Waardenburg syndrome, but is associated with a phenotype of progressive depigmentation in mice. Genomic DNA was extracted from the blood of affected and unaffected family members, and the KIT and MITF genes were sequenced. Genetic analysis of genomic DNA from both the mother and daughter with progressive piebaldism revealed a novel Val620Ala (1859T>C) mutation in the KIT gene, which was not detected in family members without progressive piebaldism or in 52 normal control individuals. This KIT mutation affects the intracellular tyrosine kinase domain and thus predicts a severe phenotype, as was the case in this family. Although other KIT mutations in the vicinity of codon 620 lead to the standard phenotype of static piebaldism, the Val620Ala mutation is novel and may result in a previously undescribed phenotype with melanocyte instability, leading to progressive loss of pigmentation as well as the progressive appearance of the hyperpigmented macules.

Myiasis in a pregnant woman and an effective, sterile method of surgical extraction.

BACKGROUND: Cutaneous myiasis caused by Dermatobia hominis involves the infestation of tissue with dipterous fly larvae and is common in many tropical and subtropical areas. We describe a patient in her sixth month of pregnancy who returned from Belize with myiasis detected in the right popliteal fossa. Multiple surgical techniques have been described in the past outlining various ways to extract the botfly larva. No single standardized technique for surgical extraction of larvae has been adopted. OBJECTIVE: To describe a highly effective, sterile method of extraction used in a pregnant patient with botfly infestation. METHODS: A combination of injection with plain 1% lidocaine, sterile occlusion with polymyxin B sulfate ointment and a cruciform incision was used to extract the larva. RESULTS: The botfly larva was easily and completely extracted without remnants of the larval body being left in the skin. CONCLUSION: The sterile technique we describe allows for quick and easy extraction of the larva without risk of secondary infection or need for antibiotics. This method is especially appropriate for pregnant patients or those with medical conditions precluding a completely competent immune response to potential secondary infection.

The pulsed dye laser for cutaneous vascular and nonvascular lesions.

The pulsed dye laser was originally developed for the treatment of vascular lesions, especially hemangiomas and port-wine stains. The central concept of pulsed-dye laser is to preserving the epidermis by allowing hemoglobin to be more precisely targeted within lesions. More recently, the pulsed dye laser has also been used in the treatment of a wide spectrum of nonvascular lesions. Because of its safety profile, and its selectivity in targeting lesions, therapists can comfortably treat a wide variety of lesions in all age groups and anatomic sites.

Image processing techniques for quantitative analysis of skin structures.

Computer-based image processing and analysis techniques were developed for quantitative analysis of skin structures in color histological sections. Performance was compared with traditional non-image processing counting methods. Skin sections were stained with Masson's trichrome, hematoxylin and eosin, picrosirius red, or one of several elastin stains. The image processing software identified the top of the cellular epidermis and the dermal-epidermal junction and then calculated the volume of the cellular layer of the epidermis, epidermal thickness, and the ratio of the dermal-epidermal junction surface area to the in-plane surface area. It also identified cells and collagen and calculated cellular densities and collagen densities in the papillary and reticular layers of the dermis. Attempts to computationally process elastin-stained sections to determine elastin density were unsuccessful. The described techniques were used in a preliminary study to compare mechanically stressed skin with control skin. Results showed significant differences in cellular density in the papillary dermis and collagen density in the reticular dermis for skin subjected to combined shear/compression or tension compared with an unstressed control. Measurements made with the computer technique and traditional technique showed comparable results; the mean difference in measurements for epidermal features was 5.33% while for dermal features it was 2.76%. Significance testing between control and experimental groups showed similar results, though for three of the 28 comparisons the computer method identified a significant difference while the traditional method did not. The computer method took longer to conduct than the traditional method, though with recent advances in computer hardware this time difference would be eliminated.

Ease of handling and clinical efficacy of fluticasone propionate Accuhaler/Diskus inhaler compared with the Turbohaler inhaler in paediatric patients. UK Study Group.

A total of 323 children aged 4-11 years who were receiving, or had symptoms indicating a clinical requirement for, inhaled corticosteroid at a daily dose of 400 micrograms budesonide (BUD) or beclomethasone dipropionate (BDP), or 200 micrograms fluticasone propionate (FP), were randomised into this multicentre, open-label, parallel group study. Patients received either FP 100 micrograms b.d. administered via the Accuhaler/Diskus inhaler (n = 159) or BUD 200 micrograms b.d. administered via a Turbohaler inhaler (n = 164) for four weeks and recorded daily their morning and evening peak expiratory flow (PEF), asthma symptoms and use of relief medication. Device handling was assessed by a questionnaire, with responses recorded on three- or five-point ordinal scales. The primary efficacy parameter was mean percent predicted morning PEF. The device handling results showed the Accuhaler/Diskus inhaler was rated more favourably than the Turbohaler inhaler in terms of ease of correct inhaler use, ease of telling how many doses were left, ease of knowing whether a dose had been inhaled and overall liking of the device. More patients in the Accuhaler/Diskus group (85%) than in the Turbohaler group (58%) said they would be happy to receive the same device again, while 8% and 25% respectively said they would not be happy to be given it again. In addition, the change from baseline to week 4 of treatment in mean percent predicted morning PEF was greater in the FP Accuhaler/Diskus group, indicating that FP 200 micrograms daily via Accuhaler/Diskus inhaler is at least as clinically effective as BUD 400 micrograms daily via the Turbohaler inhaler.

Dietary antioxidant vitamin intake and lung function in the general population.

We have investigated the relation between lung function and dietary intake of the antioxidant vitamins C and E in the general population in a cross-sectional survey of a random sample of adults from the electoral register of an administrative area of Nottingham. In 2,633 subjects 18 to 70 yr of age, we measured FEV1 and FVC, allergen skin sensitivity to grass pollen, cat fur, and Dermatophagoides pteronyssinus, pack-years smoking exposure by personal recall, and usual dietary intake of vitamins C and E by semiquantitative food frequency questionnaire. After adjustment for the effects of age, sex, height, mean allergen skin wheal diameter, and pack-years smoking history, both FEV1 and FVC were significantly and independently related to mean daily intake of vitamin C, such that a standard deviation (40 mg/d) higher vitamin C intake was associated with a 25.0 (95% CI, 5.2 to 44.8; p = 0.01) ml higher FEV1 and a 23.3 (0.94 to 45.7, p = 0.04) ml higher FVC. There was also an association between vitamin E intake and lung function, such that a standard deviation (2.2 mg) higher intake of vitamin E was associated with a 20.1 (1.3 to 40.4, p = 0.04) ml higher FEV1 and a 23.1 (1.0 to 45, p = 0.04) ml higher FVC. However, vitamin C and vitamin E intakes were significantly correlated (r = 0.29, p < 0.001), and after allowing for the effects of vitamin C there was no additional independent effect of vitamin E on either FEV1 or FVC.(ABSTRACT TRUNCATED AT 250 WORDS)

The pathology and biologic behavior of ovarian cancer. An autopsy review.

1. Widespread visceral and intestinal wall metastases are present in women dying with ovarian cancer. Intestinal wall invasion is commonly found at autopsy and is associated with bowel obstruction. Liver parenchymal replacement by metastases in more extensive than that in the lung, where most metastases have a subpleural location. Multifocality characterizes metastases in both of these organs. 2. Neoplastic lymphatic invasion is common. Lymphatic and blood vascular invasion are associated with an increased incidence of metastases in lymph nodes, small bowel wall, pancreas, lungs, ureter, and liver. 3. The mean survival time from diagnosis to death is less than 2 years. Both increasing neoplastic histological grade and clinical stage at diagnosis are associated with decreased survival time. 4. The most common causes of death are carcinomatosis, infection, or a combination of these processes. Sepsis, pneumonia, or both of these account for most of the fatal infections. 5. Bowel and ureteral obstruction constitute the most common forms of tumor-induced morbidity. The former process tends to be multifocal, involving the small and large intestines, and it is found during the disease course as well as at autopsy. Ureteral involvement is usually associated with hydronephrosis and is bilateral in approximately one fourth of the cases.

Survival time, causes of death, and tumor/treatment-related morbidity in 100 women with ovarian cancer.

One hundred cases of ovarian cancer were studied at autopsy to determine the effect of morphologic and clinical factors on survival time, the primary cause of death, and tumor/treatment-related morbidity. The mean survival time was 19 months (0 to 174 months). Increasing neoplastic histologic grade and increasing clinical stage at diagnosis were each associated with decreased survival time. In grade I tumors, the mean survival time was 84 months; in grade II tumors, it was 18 months; and in grade III tumors, it was 12 months (P = .0008). Patients who presented in stage I or II had a better survival time (28 months) than those who presented in stage III or IV (15 months) (P = .02). The most common causes of death were disseminated carcinomatosis (48%), infection (17%), pulmonary embolus (8%), and combinations of infection and carcinomatosis (11%). In patients dying of infection, 43% had sepsis, 21% had pneumonia, and 25% had a combination of sepsis and pneumonia. Escherichia coli and Klebsiella were the most common pathogens identified postmortem. Intestinal obstruction (51%) and ureteral obstruction (28%) were the most common forms of tumor-induced morbidity. Bone marrow depression and resultant pancytopenia was the most common form of treatment-induced morbidity.

Distribution of disease at autopsy in 100 women with ovarian cancer.

Clinical and morphologic factors that affected the distribution of disease are described in 100 cases of ovarian cancer at autopsy. In addition to the expected pattern of pelvic and abdominal peritoneal spread, extensive visceral parenchymal metastases were seen: liver parenchyma (45%), lung parenchyma (39%), small and large intestinal wall (52% and 55%), lymph nodes (70%), pancreas (21%), ureter (24%), bone (11%), and brain (6%). Liver parenchymal metastases replaced more than one third of the liver in 25% of cases, whereas lung metastases always involved less than one third of the lungs. When intestinal wall invasion was seen, bowel obstruction was present more often (71%) than when only intestinal serosa was involved (30%). Lymphatic invasion was predictive of lymph node, small intestinal wall, pancreatic, and liver as well as lung parenchymal metastases. Blood vessel invasion was predictive of pancreatic and ureteral metastases. Clinical stage I at diagnosis was associated with high incidences of liver parenchymal (56%), lymph node (56%), lung parenchymal (44%), large intestinal wall (33%), and bone (33%) metastases. Thus, ovarian cancer has parenchymal metastases similar to other carcinomas in addition to its peritoneal spread. Lymphatic and blood vessel invasion is predictive of such involvement. Intestinal wall invasion predicts bowel obstruction.