Skin cancer prevention campaign in childhood: survey based on 3676 children in Brazil.

BACKGROUND AND OBJECTIVES: Primary skin cancer prevention campaigns are essential and more effective among children, not only because of the importance of sun exposure effects during this period, but also because this age is when individuals are developing behaviours. The Brazilian Society of Dermatology - Regional State of Sao Paulo developed and conducted the programme named 'The Sun, Friend of Childhood', a school health education and disease prevention project for children and parents. Our objective was to evaluate the cognitive and behavioural effects of the children and parents before and after an education model-based intervention of sun protection. METHODS: We carried out a study on a school population of Social Service of Industry - Regional State of São Paulo, from the first to the fifth years of the regular course (6-10 years). Our educational project was planned to be based on two children's learning tools (comic magazine and a DVD cartoon). Questionnaires in relation to habits and knowledge in sun exposure were applied to the children (3776) before and (2748) after the intervention. A questionnaire was applied to 3663 parents regarding personal details and habits of their children. RESULTS: According to the McNemar's statistical test, all changes in the children in acquiring new knowledge about good practices for sun exposure were statistically significant. CONCLUSIONS: Educative sun exposure programmes in childhood are a relevant tool to modify the history of life for next generations, to concern the skin cancer and good health practices.

Tricistronic viral vectors co-expressing interleukin-12 (1L-12) and CD80 (B7-1) for the immunotherapy of cancer: preclinical studies in myeloma.

Synergy between interleukin-12 (IL-12) and B7-1 (CD80) for cancer immunotherapy has previously been demonstrated in animal models of breast cancer, lymphoma, and multiple myeloma. With a view to human clinical application, tricistronic retroviral and adenovirus vectors co-expressing IL-12 (IL-12p40 plus IL-12p35) and CD80 were constructed by utilizing two internal ribosome entry site (IRES) sequences to link the three cDNAs. A murine stem cell virus (MSCV)-based retroviral vector (MSCV-hIL12.B7) utilized distinct IRES sequences from the encephalomyocarditis virus (EMCV) and the foot-and-mouth disease virus (FMCV), whereas Ad5-based adenovirus vectors contained transcriptional units with two EMCV IRES sequences under the control of murine (AdMh12.B7) or human (AdHh12.B7) cytomegalovirus promoters. AdMh12.B7 was found to consistently direct higher levels of IL-12 and CD80 expression than AdHh12.B7 following infection of a number of human tumor cell lines. In preclinical studies, the human myeloma cell line U266 was infected with MSCV-hIL12.B7 and a resulting clonal cell line, U/MSCV-h12.B7, was generated with stable expression of CD80 and secreting IL-12 at 1 ng/24 h/10(6) cells. By comparison, following AdMh12.B7 infection, 81% of infected U266 cells (U/AdMh12.B7) expressed CD80 and secreted IL-12 at 25-50 ng/24 h/10(6) cells. Both engineered myeloma cell lines stimulated enhanced allogeneic mixed lymphocyte proliferation and provoked increases in cytotoxic T-lymphocyte responses and gamma-interferon release from normal donor lymphocytes exposed to parental U266 cells. These results suggest potential clinical utility of AdMh12.B7 in immunotherapy strategies for the treatment of multiple myeloma and other cancers.

A suction trephine block for marking donor corneal buttons.

We describe a technique to accurately align the circumferences of the donor button and host cornea during penetrating keratoplasty. The donor cornea is trephined on a block into which four narrow, intersecting, equally spaced radial cuts are made. Suction is applied to the donor cornea through the four cuts, resulting in four radial marks in the donor corneal epithelium. Four radial marks are also made in the host cornea before trephination, using a radial keratotomy marker. When the donor button is placed within the recipient opening, the radial marks are aligned and used as guides for the cardinal sutures. This simple technique allows for matching of the donor and host circumferences, even if there is some collapse of the peripheral host cornea and sclera at surgery, and should minimize astigmatism resulting from donor/host misalignment.

Mucous membrane grafting for severe palpebral vernal conjunctivitis.

Vernal conjunctivitis usually can be managed medically. In the rare cases that do not respond to medical treatment, surgical intervention has been considered. Four cases of vernal conjunctivitis and one case of probable contact lens-induced giant papillary conjunctivitis were treated with palpebral conjunctival excision and application of a mucous membrane graft. All patients improved symptomatically, with follow-up ranging from 1 1/2 to 14 years. The only complication encountered was recurrence of giant papillae at the conjunctiva-mucous membrane graft junction. Conjunctival excision and mucous membrane grafting is a useful procedure in rare cases of particularly severe vernal conjunctivitis.

Bright-flash electroretinography and vitreous hemorrhage. An experimental study in primates.

Serial, bright-flash electroretinograms (ERGs) were recorded from rhesus monkey eyes before and after a standard posterior penetrating ocular injury and injection of 0.5 mL of blood into the vitreous. This procedure resulted in a progressive depression to virtual nonrecordability of the ERG during a period of several weeks, owing to a combined progressive increase in optical density and loss of retinal function. The ERG depression, however, was reversible, showing a remarkable recovery during the subsequent four to eight weeks. These findings suggest that in the presence of a recent, massive vitreous hemorrhage, a nonrecordable bright-flash ERG does not necessarily indicate a permanent loss of retinal function.

Photogrammetric analysis of corneal trephination.

We used a high-magnification shadow photogrammetric system to evaluate corneal buttons trephined from human donor globes. Whole eyes were trephined with one of five instruments: nonguarded blades held by hand or placed on a handle, Barraquer-Mateus motorized trephine, Hessberg-Barron suction trephine, or Hanna microkeratotrephine. Corneoscleral buttons were punched with one of three punches: Cottingham, Katena Lieberman guillotine, or a modified Lieberman guillotine with an increased impact force (BPEI 2). The precision (how closely buttons approximated the trephine diameter), accuracy (repeatability), acircularity (deviation from roundness), and straightness (verticality of edges) of cut were calculated from the diameter and edge profile angle measurements of buttons cut by the different instruments. These results were statistically compared. The Hanna microkeratotrephine instrument had the greatest precision and accuracy, least acircularity, and straightest edges. Of the corneal punches evaluated, the Cottingham instrument had the greatest precision; however, the BPEI 2 punch cut with the greatest accuracy and the straightest edges.

Late development of ulcerative keratitis in radial keratotomy scars.

We describe three patients in whom ulcerative keratitis developed seven months to 2 1/2 years after uncomplicated radial keratotomy. All ulcers occurred along keratotomy scars within the interpalpebral fissure or inferiorly. At least one case developed spontaneously; another patient may have sustained an unrecognized corneal injury. The third patient was using an extended-wear soft contact lens for correction of residual myopia. Bacteria were isolated from two of the ulcers. With therapy, all ulcers healed without reducing visual acuity. We hypothesize that the altered structure of the slowly healing keratotomy incisions coupled with redistribution of the tear film due to changes in corneal topography may result in intermittent epithelial irregularities. Alone or in conjunction with any form of mechanical or hypoxic corneal injury, these changes along keratotomy incisions may predispose to corneal infection.

Biochemical effects of folate-based inhibitors of thymidylate synthase in MGH-U1 cells.

The TS-inhibitory effects induced by a 24-h exposure to the folate-based TS inhibitors CB3717, C2-desamino analogs of CB3717 including D1694, and BW1843U89 were quantitated using the MGH-U1 human bladder carcinoma. The effects of D1694 on the time course of TS inhibition and on intracellular deoxyuridine monophosphate (dUMP) accumulation and deoxyuridine (dUrd) production were evaluated. D1694 and BW1843U89 were the most active TS inhibitors with IC50 values of 2.4 and 0.5 nM, respectively. The C2-desamino C2-methyl dideazafolates were 27-292 times more potent than the parent CB3717 as TS inhibitors. A methyl group at the C2 position of CB3717 had the most dramatic effect, whereas a thiazole substitution for a benzyl added a small benefit and N10 substitution had a limited impact on TS-inhibitory potency and clonogenic survival. There was a significant correlation between the IC50 values for TS inhibition and those for cytotoxic potency obtained for these drugs. LV and thymidine protected cells from these folate-based TS inhibitors. Intracellular dUMP levels following 24 h D1694 (IC50) exposure increased 7-fold. Levels of dUrd effluxing into the media increased up to 4.5 microM following a 24-h exposure to D1694 (IC90). We conclude that (a) C2-desamino C2-methyl dideazafolates are potent TS inhibitors, (b) TS inhibition requires prolonged exposure with these folate TS inhibitors, (c) survival is correlated with inhibition of TS for the folate-based TS inhibitors and (d) the biochemical consequences of TS inhibition include increased dUMP and dUrd levels.

Improved therapeutic outcome following combination immunogene vaccination therapy in murine myeloma.

Increasing evidence suggests a role for immunologic vaccination and therapy in the management of minimal residual myeloma. We have previously demonstrated a synergistic effect of combining the Th1 stimulating cytokine IL-12 with the co-stimulatory molecule CD80 in murine myeloma vaccination therapy. We reasoned that the efficacy of such treatment might be further improved by incorporating additional gene products which enhance the function of antigen presenting cells. Studies were therefore conducted with murine myeloma BM1 cells expressing Flt3L (membrane bound or soluble forms) or GM-CSF and the IL-12 x CD80 combination. Single agent and combined therapeutic approaches were explored. All gene-modified BM1 cells, except BM1/IL-12 x CD80, developed tumors when subcutaneously injected into BALB/c mice. As prophylactic tumor vaccines, the combined use of gene-modified BM1/sFlt3L+GM-CSF+IL-12 x CD80 was most effective, providing 100% protection against subsequent parental BM1 tumor challenge. By comparison, only partial protection was observed with any single gene-engineered tumor vaccine. Notably, IL-12 x CD80 coexpressing BM1 cell vaccines were the most effective therapeutic vaccine in a minimal disease model. Such protective vaccination was achieved by stimulation of lymphocyte proliferation and enhancement of cytotoxic lymphocyte activity.

Relationship of antisperm antibodies to oocyte fertilization in in vitro fertilization-embryo transfer.

Antisperm antibodies (ASA) appear to impair reproduction; however, their clinical significance in in vitro fertilization-embryo transfer (IVF-ET) is unestablished. For examination of this question, the immunobead binding technique was used to identify IgA, IgG, and IgM ASA in the serum, semen, and follicular fluid (FF) of 40 couples undergoing IVF-ET. ASA binding to sperm tail tip did not predict the fertilization rate of uniformly inseminated mature oocytes. Similarly, ASA binding to sperm head in semen and male serum did not predict fertilization. However, the fertilization rate in couples with ASA to sperm head (ASA-H) of at least one isotype in female serum (n = 6) was significantly less than in those without ASA-H (n = 34; 34% versus 74%, P less than 0.01). Among these women, oocyte fertilization rates were 33% versus 71% (P less than 0.001). Sixty percent of women whose ova did not fertilize (n = 5) had ASA-H in their serum versus 6% of those whose ova did (n = 35; P less than 0.05). The presence of ASA-H in FF also correlated with fertilization. ASA-H in female serum reduced the zygote cleavage rate from 91% to 67% (P = 0.51). We conclude that the presence of ASA-H in female serum and FF is associated with reduced fertilization in IVF-ET.

Bacterial endophthalmitis resulting from radial keratotomy.

Staphylococcus epidermis endophthalmitis developed nine days after surgery in a 47-year-old man who underwent a 16-incision radial keratotomy during which the cornea was inadvertently perforated. The anterior chamber showed marked cellular reaction and flare and there was a 5% hypopyon inferiorly. There was also a marked cellular reaction in the vitreous, which contained many fluffy white balls. Visual acuity decreased to counting fingers at 1 foot. A pars plana vitrectomy and intraocularly, periocularly, intravenously, and topically administered antibiotics resulted in recovery of the visual acuity to 6/9 (20/30).

Potential bacterial contamination in fluorescein-anesthetic solutions.

To determine the ability of fluorescein-anesthetic combination solutions and their applicators to regain sterility, we contaminated four commercially available fluorescein-anesthetic solutions and their dropper tips with inocula of either Pseudomonas species or Staphylococcus species. No organisms could be cultured from Fluress one minute after inoculation of the solution or five minutes after inoculation of the dropper tip. In contrast, organisms were cultured from the other fluorescein-anesthetic preparations for at least one hour after bacterial inoculation into the solution or onto the dropper tip. These differences in the ability of fluorescein-anesthetic solutions to regain sterility after bacterial contamination were statistically significant.

Preliminary report on corneal incisions created by a hydrogen fluoride laser.

We created corneal incisions in eye bank eyes with a pulsed hydrogen fluoride infrared laser. This laser was selected because its emission spectrum (2.7 to 3.0 micron) closely corresponds to the absorption peak of water in the infrared region. Short pulses (200 nsec) of hydrogen fluoride laser light focused with a cylindrical lens resulting in radiant exposures of 1.3 J/cm2 at the corneal surface created linear cuts in the cornea with minimal thermal damage adjacent to the incision, suggesting that the pulsed hydrogen fluoride laser may be useful for corneal surgery.

Noncontact trephination of the cornea using a pulsed hydrogen fluoride laser.

We used a pulsed hydrogen fluoride infrared laser and a specially designed axicon lens to perform circular corneal trephinations in ten eye bank eyes. This noncontact system focused each laser pulse into an annulus on the cornea. Corneal perforation was achieved in seven to nine seconds at a repetition rate of 10 Hz, using a laser output energy of 100 mJ per pulse. A trephination, 90% of corneal thickness, 6.5 mm in diameter, was produced with 70 pulses.

Ulcerative keratitis associated with contact lens wear.

A review of 573 cases of ulcerative keratitis cultured at the Bascom Palmer Eye Institute from January 1977 through September 1982 showed that 118 cases (21%) were associated with contact lens wear; of these, 64 were culture-positive. Of these culture-positive cases, 50 (78%) were caused by gram-negative bacteria, nine (14%) by gram-positive organisms, and two (3%) by fungal organisms. Of the 264 culture-positive ulcers not associated with contact lens wear, 119 (45%) were caused by gram-negative bacteria, 74 (28%) by gram-positive organisms, and 63 (24%) by fungal organisms. These statistically significant differences suggested that the organisms associated with ulcerative keratitis within our geographic region are modified by contact lens use. Pseudomonas was the organism most frequently isolated from ulcers associated with contact lenses and was responsible for nearly two thirds of the culture-positive cases.

Granular epithelial keratopathy as an unusual manifestation of Pseudomonas keratitis associated with extended-wear soft contact lenses.

We describe four patients who, using extended-wear soft contact lenses for myopia, abruptly developed ocular irritation and injection associated with elevated granular opacities initially confined to the central corneal epithelium. Cultures of the granular epithelial lesions were positive for Pseudomonas aeruginosa in all patients. Cultures of the contact lenses and lens case solutions grew Pseudomonas species and other gram-negative organisms. All patients responded to discontinuation of lens wear and frequent topical antibiotics. All recovered baseline visual acuity, and three have successfully resumed contact lens wear. These cases document that Pseudomonas keratitis may be manifested as a granular epithelial keratopathy.

Process-centered revenue-cycle management optimizes payment process.

By implementing a process-centered revenue cycle, healthcare organizations and group practices can achieve a seamless payment process with clear lines of accountability to achieve target outcomes. The integrated, end-to-end, revenue-cycle process involves four key components: jobs, skills, staffing, and structure; information and information systems; organizational alignment and accountability; and performance measures and evaluation measures. The Henry Ford Health System (HFHS), based in Detroit, Michigan, exemplifies the type of results that are achievable with this model. HFHS includes a group practice with more than 1,000 physicians in 40 specialties. After implementing a process-centered revenue cycle, HFHS dramatically improved registration and verification transactions and optimized revenues.