Physical and chemical stability of proflavine contrast agent solutions for early detection of oral cancer.

BACKGROUND AND PURPOSE: Proflavine hemisulfate solution is a fluorescence contrast agent to visualize cell nuclei using high-resolution optical imaging devices such as the high-resolution microendoscope. These devices provide real-time imaging to distinguish between normal versus neoplastic tissue. These images could be helpful for early screening of oral cancer and its precursors and to determine accurate margins of malignant tissue for ablative surgery. Extemporaneous preparation of proflavine solution for these diagnostic procedures requires preparation in batches and long-term storage to improve compounding efficiency in the pharmacy. However, there is a paucity of long-term stability data for proflavine contrast solutions. METHODS: The physical and chemical stability of 0.01% (10 mg/100 ml) proflavine hemisulfate solutions prepared in sterile water was determined following storage at refrigeration (4-8℃) and room temperature (23℃). Concentrations of proflavine were measured at predetermined time points up to 12 months using a validated stability-indicating high-performance liquid chromatography method. RESULTS: Proflavine solutions stored under refrigeration were physically and chemically stable for at least 12 months with concentrations ranging from 95% to 105% compared to initial concentration. However, in solutions stored at room temperature increased turbidity and particulates were observed in some of the tested vials at 9 months and 12 months with peak particle count reaching 17-fold increase compared to baseline. Solutions stored at room temperature were chemically stable up to six months (94-105%). CONCLUSION: Proflavine solutions at concentration of 0.01% were chemically and physically stable for at least 12 months under refrigeration. The solution was chemically stable for six months when stored at room temperature. We recommend long-term storage of proflavine solutions under refrigeration prior to diagnostic procedure.

Triple dye plus rubbing alcohol versus triple dye alone for umbilical cord care.

Current practices for umbilical cord care vary across centers, but the evidence regarding these practices and their impact on cord separation, complications, and health care use are limited. The objective of this study was to compare the effect of triple dye alone (brilliant green, crystal violet, and proflavine hemisulfate) versus triple dye plus rubbing alcohol (isopropyl alcohol) twice daily on time to umbilical cord separation, complications, and health care use. For the 90 newborns who completed the study, there were no significant differences between treatment groups for time to cord separation, cord-related morbidities, or cord-related urgent care. Based on these study results, there does not appear to be significant benefit to the addition of twice daily applications of rubbing alcohol to neonatal umbilical cords following triple dye treatment after birth.

A randomized study of 3 umbilical cord care regimens at home in thai neonates: comparison of time to umbilical cord separation, parental satisfaction and bacterial colonization.

OBJECTIVE: To compare time to cord separation, parental satisfaction and bacterial colonization, among 3 regimens of cord care at home. STUDY DESIGN: Randomized controlled trial. MATERIAL AND METHOD: Term infants were randomly assigned based on cord care regimens at home: 1) triple dye, 2) alcohol, and 3) no antiseptic agent. Timing of cord separation, and parental satisfaction were evaluated during the first month of age. RESULTS: 185 infants were recruited. Time to cord separation in infants of group I was significantly longer than in group 2 (p = 0.036) and group 3 (p = 0.003). The satisfaction scores of group I were significantly lower than those of group 2 and group 3. 180 culture specimens were performed and positive in all but none had omphalitis. CONCLUSION: Triple dye delayed time to cord separation and was less satisfactory. The authors conclude that using alcohol or dry clean could be alternative ways of umbilical cord care at home.

Management of ventral hernia after giant exomphalos with external pressure compression using helmet device.

PURPOSE: The aim of this study was to evaluate an alternative technique of reducing a ventral hernia that follows the primary conservative treatment of a giant omphalocoele. METHODS: The patient is a full-term male neonate with a giant exomphalos. Initially triple dye was applied as an eschar-inducing agent. This resulted in a ventral hernia after 1 month. It was decided to achieve expansion of the abdominal cavity based on the principle of external pressure compression using a sphygmomanometer cuff over the hernia. The cuff was worn continuously, and manual pressure was applied daily. Care was taken to avoid intraabdominal hypertension using the reading of the manometer that was attached. The external pressure was corroborated with observations of respiration and circulation. RESULTS: The child did not show any ill effects of raised intraabdominal pressure. Throughout the treatment, the child was on full oral feedings and did not require any ventilator support. Reduction of the ventral hernia was achieved in 9 months. Surgical repair of the residual hernia defect was carried out by double breasting of the fascia. CONCLUSIONS: The application of controlled external pressure using a specially constructed device is a safe, noninvasive, and effective method of achieving reduction of a ventral hernia after primary conservative treatment of a giant omphalocoele.

Randomized trial of alcohol versus triple dye for umbilical cord care.

Over a 4-month period, all infants admitted to the well-baby nursery were enrolled in a prospective study designed to compare cord separation times between infants treated with triple dye once, followed by daily alcohol application, to infants treated with daily alcohol application alone. Follow-up phone calls were done 7 days after discharge, with weekly calls until cord separation occurred. The objective was to determine whether the umbilical cord care regimen of triple dye followed by alcohol has an advantage over the alternative regimen of alcohol alone, with regard to cord separation, parenting, or healthcare caretaker preferences. In total, 634 infants were enrolled, with 599 infants (94%) completing the study. Infants in the alcohol alone group had a shorter cord separation time by 3 days (10 versus 13 days) (p < 0.0001). There was no reported increase in infection, and monetary savings were noted. We conclude that alcohol applied once a day appears to be a safe and effective means of promoting cord detachment.

[Control of staphylococcal skin infections in a nursery].

Outbreaks of skin infections due to Staphylococcus aureus continue to be a major problem in newborn nurseries. In this report, we described how the staphylococcal skin infections were controlled in the nursery during the last 5 1/2 years. An outbreak of staphylococcal skin infection (totally 29 cases) developed in January 1985, and declined dramatically to 3 cases in March of the same year when 3% hexachlorophene (HCP) bathing was used (period 1-January 1985 to March 1985). The infections increased to 30 cases in May when HCP bathing was discontinued and was replaced by baby soap baths (period 2-April 1985 to May 1985). Once again, HCP bathing (period 3-June 1985 to January 1987) was reinstituted and infection rate was reduced. After discontinuation of HCP (period 4-February 1987 to March 1987), another outbreak of staphylococcal skin infection reappeared. It was controlled again with HCP bathing (period 5-April 1987 to April 1988). Daily baby soap baths were continued during period 6 (May 1988 to October 1988), and skin infections increased again. Finally in period 7 (November 1988 to June 1990), daily baby soaps were reinstituted and a triple dye was applied daily to the cord and to the surrounding skin (1 inch diameter) until discharge. During this period, staphylococcal skin infections was reduced to 1-4 cases and no more outbreaks occurred. Our data confirmed that 3% HCP bathing of newborns reduced the infection rate of Staphylococcus aureus during an endemic period, and supported that triple dye may be an alternative to HCP for preventing staphylococcal skin infection in a newborn nursery.

[A new method of therapy for branchiobdellosis in crayfish]. / Nový zpusob lécení branchiobdelózy raku.

Crayfish (Astacus fluviatilis Fabricius, 1793) were treated three times with a bath of diluted ammonia water and proflavine for four and six minutes at a temperature of 18 degrees C to get rid of the ectoparasitic worms of Branchiobdella parasita Henle, 1835; the hatching ability of the Branchiobdella parasita eggs was stopped after the treatment. No lethal effect of the bath on the crayfish of 5 to 14 cm was observed, the lethal effect on the young crayfish borne on the uropods of the female crayfish cannot be eliminated: during the baths the young crayfish died (the death rate was approximately 6% of the average fertility of crayfish); the young crayfish may have been damaged during the treatment operations with the crayfish. The bath of diluted ammonia water and proflavine may be recommended for the treatment of branchiobdellosis in crayfish to be planted, or after several-hour storage of crayfish supplied to the market. One replication of the above cycle is sufficient according to the results obtained. The ammonia content in the ammonia water depends also on the duration of storage and on the storage temperature--it can drop during the storage. Therefore the ammonia water should be used as soon as possible after the despatchment from the place of production; the ammonia content should be determined by means of titration before preparing the bath, and according to this content the dilution ratio should be adjusted.

Treatment of genital herpes simplex virus infection with photodynamic inactivation.

A double-blind randomized study to evaluate the effect of proflavine in the treatment of genital herpesvirus infection was conducted. One hundred fifty-seven women were studied, of whom 75 were treated with proflavine (treated women) and 82 were treated with placebo (control group). There were 62 women with primary disease and 95 with recurrent infection. Under the conditions by which this study was conducted, there was no apparent difference in the time of healing of lesions, development of recurrences, or virus isolation following treatment in the proflavine-treated and control groups.

In vitro and in vivo photosensitized inactivation of dermatophyte fungi by heterotricyclic dyes.

The ability of three heterotricyclic dyes to photosensitize dermatophyte fungi was studied with Trichophyton mentagrophytes and Microsporum gypseum. In vitro studies showed that methylene blue, neutral red, and proflavine were capable of killing these fungi when used in conjunction with broad-spectrum light. Proflavine, however, killed both fungi most rapidly and was used for further studies. Fungal killing by proflavine plus light was dependent on dye concentration, pH, light wavelength, and light intensity. Based on the in vitro studies, a treatment regimen was developed for in vivo use on experimentally infected animals. When treatment of guinea pigs inoculated with T. mentagrophytes was begun during fungal invasion, lesion formation at inoculated sites was either prevented or substantially reduced. When treatment was begun after lesion formation, however, light-plus-dyed treated sites showed only slightly faster curing than untreated sites.

[Elimination of multiple drug resistance of intestinal bacteria in white mice in vivo with proflavine and rimactan]. / Eliminirane na mnogolekarstvena ustoichivost na chrevni bakterii u beli mishki in vivo s proflavin i rimaktan.

Albino mice, infected with 0.4 cu. cm of 10(10) microbial cells (S. Heidelberg), were treated with proflavin (0.4 cu. cm of a 0.3% solution) and rimactan rifamycin SV (0.4 cu. cm of a 0.4% solution). Proflavin was given singly and four times, daily, in the course of four days, and rimactan was applied four times. Given in a single dose proflavin was found to prolong twice as long the life span of albino mice infected with S. heidelberg. When injected four times it lowered considerably the mortality rate among the animals, the percent of survivals being 62. It was shown to hinder the transmission of multidrug resistance to the normally existing intestinal microflora. It also eliminated the multidrug resistance that intestinal bacteria had acquired in the course of the first several days of drug application. The action of rifamycin proved stronger: 83% of the albino mice treated survived. It eliminated the markers of resistance--both the acquired ones and those carried by the normal recipients (intestinal bacteria)--that substantiated multidrug resistance as well as some of the markers of the donor itself (S. heidelberg).

[Herpes simplex virus (hsv-1 and hsv-2) infection: its clinical and oncogenic properties (author's transl)]. / Die Herpes-simplex-Virus-(HSV-1-und HSV-2-) Infektion- ihre klinische und onkogene Bedeutung.

The epidemiology and clinical features of diseases caused by the herpes simplex virus, are reviewed and recent results are discussed which give an insight into the complex mechanism of primary and chronic, recurrent HSV-1 infections. Immunological reactions in HSV infection and data concerning the oncogenic potential of HSV-1 and -2 are dealt with. Furthermore, current therapeutic possibilities are outlined.

Group B beta-hemolytic streptococcal colonization. Acquisition, persistence, and effect of umbilical cord treatment with triple dye.

Following an outbreak of group B beta-hemolytic streptococcal neonatal infection (GBS), a prevalence survey of GBS colonization was performed on 238 infants. No important differences were noted in the prevalence of colonization when the infants were grouped according to age. Follow-up of 24 colonized babies for three months disclosed that most had persistence of GBS at the rectum and pharynx. Local umbilical cord care with triple dye (TD) or hexachlorophene skin cleanser was compared with untreated controls with respect to rates of GBS colonization. At birth the colonization rates of the three groups were similar. The rate of acquisition of colonization with GBS was 1.0% in the TD group, 6.3% in the hexachlorophene group, and 8.3% in the control group. Triple dye was much more effective than no specific cord care or hexachlorophene in preventing acquisition of GBS colonization.

Photodynamic inactivation of verrucae vulgares. I.

Verrucae vulgares (v.v.) stained in vivo and in vitro with 0.1% and 1% proflavine in 100% dimethylsulphoxide (DMSO) and 0.1% and 1% neutral red in 100% DMSO were examined grossly and by fluorescence microscopy. Light transmission studies were made using both whole v.v. embedded in methacrylate and 5 micrometer frozen sections. The dyes were seen to penetrate to the epidermal and dermal structures in the in vivo stained v.v. and accumulate in the cell nuclei. The average concentration of neutral red in the v.v. was estimated to be 2 X 10(-5) M. The concentration of proflavine was lower than that, but exceeded 10(-6)M. There was diffuse staining throughout the in vitro stained warts. From 400-600 nm the warts were penetrated by at least 1% of the light directed toward their surfaces.

Photodynamic inactivation of verrucae vulgares. II.

Photodynamic inactivation therapy, consisting of a double-blind, paired comparison treatment schedule, was used in treating 56 patients for recalcitrant, symmetrical verrucae vulgares. 0.1% proflavine in 100% dimethylsulphoxide (DMSO) and 0.1% neutral red in 100% DMSO were used as active dyes, and 1% picric acid in 100% DMSO and 1% color ruber in 100% DMSO and 1% color ruber in 100% DMSO served as corresponding placebos. A Westinghouse sunlamp and black light were used to irradiate the warts dyed with proflavine and its placebo, and the warts dyed with neutral red and its placebo were irradiated with an ordinary light bulb (Osram 588597). 50 patients completed the treatment. 10 of the 27 patients treated with proflavine and 10 of the 23 patients treated with neutral red were cured by the end of an 8 week period, with the warts disappearing simultaneously from the actively as well as the placebo-treated side. Complement fixing antibodies against wart virus were detected in one of the cured patients and 2 who were treatment failures.