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Effect of dexamethasone on lymphocyte subpopulations in premature infants with bronchopulmonary dysplasia.

OBJECTIVE: This study was designed to determine the effect of dexamethasone treatment on peripheral blood lymphocyte counts and subpopulations in premature infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Peripheral blood lymphocyte subpopulations in 12 premature infants with BPD were analyzed before treatment with a 6-week course of dexamethasone (day 0), on days 3 and 10 of treatment, and 2 weeks after discontinuing dexamethasone therapy (day 56). Lymphocyte immunophenotypes were determined using direct two-color immunofluorescent staining followed by flow cytometry. RESULTS: The percentage of lymphocytes was significantly lower on days 3 (17.55 +/- 2.55) and 10 (20 +/- 11.8) of dexamethasone therapy compared with before (30.36 +/- 6.41) or after treatment. The percentage of T cells was significantly lower on days 3 and 10 of dexamethasone therapy (mean +/- SEM; 58.09 +/- 1.93 and 60.09 +/- 2.47, respectively) compared with before (67.09 +/- 4.24) or after treatment. The absolute number of T cells was significantly lower on day 10 of therapy. The percentage of CD4+ cells was significantly lower on days 3 (38.91 +/- 2.49) and 10 (40.45 +/- 2.24) of therapy, and this decrease persisted after dexamethasone was stopped (36.73 +/- 3.41). The absolute number of CD4 cells was significantly lower on day 10 (1328 +/- 216) of therapy and reached a nadir on day 56 (1143 +/- 106). Similarly, the CD4/CD8 ratio was also significantly lower on days 3 and 10 of treatment (1.56 +/- 0.18 and 1.64 +/- 0.14, respectively) and reached a nadir on day 56 (1.04 +/- 0.13). CONCLUSION: Dexamethasone significantly reduced the percentage and absolute number of lymphocytes, T cells, and CD4 cells, as well as the CD4/CD8 ratio. A reduction in CD4 cells and in the CD4/CD8 ratio persisted 2 weeks after dexamethasone therapy was stopped. In contrast, the absolute number of B cells increased transiently, and CD8 cells were unaffected by dexamethasone. This alteration in lymphocyte subpopulations may help account for the clinically beneficial anti-inflammatory effect of dexamethasone in the treatment of BPD complicated by respiratory failure. The dexamethasone-induced decrease in CD4 cells may also increase the susceptibility of these infants to infection.

B-Lymphocytes↗

Photodynamic therapy and indocyanine green guided feeder vessel photocoagulation of choroidal neovascularization secondary to choroid rupture after blunt trauma.

PURPOSE: To describe photodynamic therapy (PDT) and additional indocyanine green (ICG) guided feeder vessel photocoagulation as a treatment of choroidal neovascularization (CNV) secondary to choroidal rupture in case of blunt head trauma. DESIGN: Interventional case report. METHODS: A 61-year-old woman developed subfoveal CNV originating from a choroid tear 8 years after blunt head trauma. Four sessions of PDT were applied and an additional two consecutive sessions of selective ICG-guided feeder vessel photocoagulation conducted. RESULTS: Transient reduction of leakage and closure of feeder vessels could not prevent further growth of the CNV. CONCLUSIONS: PDT reduced leakage temporarily and additional ICG-guided feeder vessel photocoagulation closed treated feeder vessel and CNV. New feeder vessel formation and growth of CNV in case of traumatic choroid rupture could not be treated effectively by these two laser treatment modalities to prevent severe deterioration of visual acuity.

Choroid↗

Future directions of laser phototherapy for diagnosis and treatment of malignancies: fantasy, fallacy, or reality?

A new and highly promising adjunctive modality for the diagnosis and therapy of malignancies is under development using lasers and tumor targeting dyes. To reach the eventual goal of clinical treatment, several current "fantasies and fallacies" regarding laser applications in medicine must be identified and their problems clearly outlined. A multidisciplinary scientific approach is also required to enable the clinical practicality of this laser targeting approach. Many new dyes and laser wavelengths are being tested to improve specific tumor uptake and/or retention, lower systemic toxicity, increase tissue penetration, and identify fluorochromes with synergistic properties to further enhance laser tumoricidal effects. Rapid technological advancements in magnetic resonance imaging may now provide an extremely sensitive way to detect and monitor laser-tissue effects, and allow efficient interstitial laser phototherapy of deep and sometimes inaccessible tumors. The current and future prospectives of the emerging field of laser phototherapy are described.

Coloring Agents↗

[Changes in prostatic circulation in response to laser therapy and magnetic therapy in patients with benign prostatic hyperplasia].

The results of preoperative preparation were analysed in 59 patients with prostatic benign hyperplasia (PBH) subjected to TUR. Treatment outcomes were assessed by transrectal ultrasound (color Doppler mapping) in two groups of patients. Group 1 received combined therapy including transrectal laser radiation of the prostate, group 2--transrectal magnetotherapy. The analysis showed that laser radiation reduced insignificantly the size of the prostate and adenomatous node, improved microcirculation and circulation in the prostate. This resulted in relief of inflammation and reduction of the number of postoperative inflammatory complications. Transrectal magnetotherapy has a positive effect on vascularization and hemodynamics of the prostate, local immunity, contamination of the tissues with pathogenic flora.

Aged↗

Prognostic factors in resectable pancreatic cancer: p53 and bcl-2.

The p53 tumor suppressor gene and the Bcl-2 proto-oncogene regulate cell cycle progression and apoptosis. We evaluated the expression of these molecular markers with standard pathologic prognostic variables in patients who received multimodality therapy for resectable adenocarcinoma of the pancreas to study the effect of p53 and Bcl-2 on survival duration. Immunohistochemical staining of archival material was performed to determine levels of expression of p53 and Bcl-2 proteins in 70 patients with adenocarcinoma of pancreatic origin. All patients underwent a potentially curative pancreaticoduodenectomy and standardized pathologic analysis of resected specimens. Potential pathologic and molecular prognostic variables were assessed for their effect on survival duration. Nuclear staining for p53 was observed in 33 (47%) of 70 specimens. Immunostaining for Bcl-2 was observed in 23 specimens (33%). A trend toward improved survival duration was seen in patients whose tumors stained positive for either p53 or Bcl-2. Negative staining for both markers predicted short survival (P = 0.01). By univariate and multivariate analyses, no single pathologic factor was associated with survival duration. Immunohistochemical staging using both p53 and Bcl-2 significantly predicted survival duration by univariate and multivariate analysis; patients whose tumors stained positively for p53 and/or overexpressed Bcl-2 had a significantly longer survival than those whose tumors stained negative for both proteins.

Adenocarcinoma↗

A standardized approach for iris color determination.

Latanoprost, the phenyl-substituted prostaglandin F2alpha, has been found to be an effective agent for glaucoma therapy. This prostaglandin derivative exerts ocular hypotensive activity but is also associated with an untoward side effect, namely iris color changes. Latanoprost provoked iris color changes in cynomolgus monkeys and in multicenter clinical trials. Until now photographs were taken and compared with color plates to document these changes. The disadvantage of this method is obvious, i.e., the color luminance varies between measurements due to changes in the developer. Furthermore, subjective comparison of color changes relative to color plates rendered judgment subject to impression and opinion rather than to objective data. Therefore, a computerized method using a 3-CCD video camera attached to a slit lamp was developed. The signals were transferred to a computer and a single frame, which was "frozen" by means of a "grabber card." Camera and the computer had previously been calibrated and color plates were measured to check the standard conditions. They were evaluated by a software program displaying average color (as red, green, and blue values) of the selected area. This method provides a fast and accurate way to quantify color changes in the iris of both experimental animals and clinical trials.

Animals↗

Enhanced efficacy of gemcitabine in combination with anti-CD20 monoclonal antibody against CD20+ non-Hodgkin's lymphoma cell lines in vitro and in scid mice.

BACKGROUND: Despite exciting new targeted therapeutics against non-Hodgkin's lymphoma (NHL), chemotherapy remains a cornerstone of therapy. While purine nucleoside analogs have significant activity in low grade NHL, the pyrimidine nucleoside analog gemcitabine has been less extensively studied, but has important activity. Use of the anti-CD20 monoclonal antibody rituximab in combination with chemotherapy for B-NHL is becoming prevalent in clinical practice, but has not been extensively studied in pre-clinical models. METHODS: We have tested the activity of gemcitabine +/- rituximab in vitro and in scid/human NHL xenograft models. We used two t(14;18)+, CD20+ follicular B cell NHL cell lines, DoHH2 a transformed NHL line and WSU-FSCCL isolated from pleural fluid of a patient with indolent NHL. RESULTS: Gemcitabine is cytotoxic to DoHH2 and WSU-FSCCL cells in vitro, and the IC50 is 2-3 fold lower in the presence of rituximab. Apoptosis is also enhanced in the presence of rituximab. Clearance of NHL cells from ascites in scid mice is prolonged by the combination, as compared with either agent alone. Most importantly, survival of scid mice bearing human NHL cells is significantly prolonged by the combination of gemcitabine + rituximab. CONCLUSION: Based on our pre-clinical data showing prolonged survival of mice bearing human lymphoma cell line xenografts after treatment with gemcitabine + anti-CD20 antibody, this combination, expected to have non-overlapping toxicity profiles, should be explored in clinical trials.

Animals↗

Effect of hyperthermia on the cytotoxicity of 4 chemotherapeutic agents currently used for the treatment of transitional cell carcinoma of the bladder: an in vitro study.

PURPOSE: Hyperthermia combined with chemotherapy is not a novel cancer treatment. However, the working mechanism of this combination therapy is not fully understood. In the current in vitro study we investigated the differences in cytotoxicity of 4 chemotherapeutic agents at 37C or 43C. MATERIALS AND METHODS: The human transitional cell carcinoma cell lines used were RT4, RT112, 253J and T24. Cells were seeded in 96-well microtiter plates. After 24 hours cells were treated for 60 minutes with increasing concentrations of mitomycin C, epirubicin, gemcitabine and EO9 at a temperature of 37C or 43C. After treatment cells were rinsed 3 times and left for 24 hours in the incubator at 37C. The influence of chemotherapy and temperature on cell survival was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay. RESULTS: Decreased cell proliferation with increasing concentrations of chemotherapeutic agents was demonstrated. EO9 proved to be the most potent agent at each temperature. Hyperthermia alone did not demonstrate decreased cell proliferation. However, a synergistic effect on decreased cell proliferation was demonstrated in all cell lines and chemotherapeutic agents used, although each had a maximum at a different chemotherapy concentration and to a different extent. Synergism was most obvious in cell lines treated with low dose epirubicin. CONCLUSIONS: Synergism with hyperthermia and chemotherapy was clearly demonstrated for epirubicin, EO9, mitomycin C and to a lesser extent gemcitabine. Hyperthermia alone did not cause decreased cell proliferation. Synergism was most prominent with low drug doses and the most potent drug used in this in vitro study was EO9.

Antibiotics, Antineoplastic↗

Major suppression of pro-alpha1(I) type I collagen gene expression in the dermis after keloid excision and immediate intrawound injection of triamcinolone acetonide.

BACKGROUND: A keloid is a benign tumor that contains excess collagen, primarily type I collagen. A common therapy is intralesional injection of a glucocorticosteroid, such as triamcinolone acetonide (TA). Surgical excision is also common; often a glucocorticosteroid is injected weeks after excision when wound repair has already begun. OBJECTIVE: Our purpose was to determine the efficacy of TA in reducing the pro-alpha1(I) type I collagen mRNA in the dermis, when TA is injected into the wound bed immediately after surgical excision of the keloid. METHODS: Six patients with previously untreated keloids were studied. Three were treated with 10 mg/ml of TA immediately after excision of the keloid (experimental group); the other three patients were not treated with TA until 2 weeks after excision (control). Punch biopsy specimens were obtained from the TA-treated sites 2 weeks after removal of the keloid and from the wounds of the control group of patients before they were treated with TA. Sections were prepared for in situ hybridization analysis of the pro-alpha1(I) collagen mRNA, as well as for histochemical analysis of collagen fibers. RESULTS: All keloids showed greatly elevated levels of pro-alpha1(I) type I collagen mRNA in the dermis. Postsurgical wounds injected with TA after removal of the keloid expressed decreased pro-alpha1(I) collagen transcripts, compared with skin not treated with TA. The collagen bundles were also thinner and less dense in the TA-treated skin. CONCLUSION: Downregulation of the type I collagen gene expression is elicited by immediate TA injection after keloid excision. This suggests that prevention of recurrent keloid growth is possible if surgical excision is accompanied by immediate TA injection into the wound bed and that healing of the wound is not apparently compromised by inhibition of type I collagen gene expression.

Administration, Topical↗

Use of ultrasound biomicroscopy, indocyanine green angiography and HLA-B51 testing as adjunct methods in the appraisal of Behçet's uveitis.

PURPOSE: Behçet's uveitis is not common in western Europe and the disease presentation is less obvious than in "endemic" countries such as Turkey and Japan. This makes the diagnosis more difficult. Early diagnosis is important, as the prognosis is better if therapy is started early. New methods such as ultrasound biomicroscopy (UBM) and indocyanine green angiography (ICGA) can improve the characterisation and diagnosis of uveitis. Our purpose was to present our experience with these new methods as well as HLA-B51 testing in the appraisal of patients with Behçet's uveitis. PATIENTS AND METHODS: Patients seen by the authors between 1997 and 2001 with Behçet's uveitis or suspected Behçet's uveitis and who underwent ICG angiography or UBM were included. Symptoms and signs, results of laboratory work-up including HLA-B51 antigen testing and the delay to diagnosis, were analysed. Fluorescein and ICG angiography and UBM testing were performed according to standard protocols used for uveitis patients and their contribution towards diagnosis and management were analysed. RESULTS: Uveitis was non granulomatous in all patients. Fluorescein angiography showed moderate to severe diffuse retinal vasculitis compatible with Behçet's uveitis in all cases. HLA-B51 testing was positive in 5 of 7 tested cases, being useful to orient the diagnosis. UBM contributed to the diagnosis in all five tested cases, being the determining element in 3 patients. It allowed redirection of the diagnosis from pars planitis to Behçet's in 2 patients with poorly transparent media because it failed to show the typical pars planitis deposits. In a case originally diagnosed as Behçet's it allowed correction of the diagnosis to pars planitis because of the presence of the typical UBM pars plana depositis. ICG angiography allowed detection of choroidal vasculitis in all five tested cases. CONCLUSIONS: In Behçet's patients who did not present with a full-blown clinical picture, as they are often seen in non-endemic areas, UBM examination and HLA-B51 testing were valuable additional diagnostic elements helping to redirect the diagnosis correctly and to reduce the diagnostic delay in these patients. The hitherto unknown choroidal vasculitis shown by ICG angiography in all five investigated patients indicates that choroidal involvement probably occurs in most newly diagnosed Behçet's patients.

Adolescent↗

Photodynamic therapy with verteporfin for peripapillary choroidal neovascularization.

PURPOSE: To evaluate the efficacy of photodynamic therapy with verteporfin in the management of symptomatic extrafoveal peripapillary choroidal neovascularization (CNV). METHODS: Seven eyes of seven patients with symptomatic peripapillary CNV underwent visual acuity testing, ophthalmic examination, color photography, and fluorescein angiography to evaluate the results of photodynamic therapy with verteporfin. Patients were offered treatment following the development of hemorrhage, subretinal fluid, or lipid if it was associated with visual symptoms. A standard nomogram was used to dose Visudyne, application was performed in three separate 30-second zones confluent over the extent of the lesion. The light dose per unit area applied to the retina was approximately 18 J/cm. RESULTS: Five of the seven had CNV limited to the peripapillary area associated with age-related macular degeneration; the remaining two eyes had presumed ocular histoplasmosis syndrome. In five of the seven eyes, two treatments were needed and in two eyes only one treatment was necessary to elicit resolution of active leakage. Retreatment was performed at an average of 76 days after initial treatment. Baseline best-corrected visual acuity (BCVA) ranged from 20/20 to 20/150. Final BCVA ranged from 20/20 to 20/80. In all eyes except for one, which had a pretreatment vision of 20/20, at least two lines of Snellen visual acuity improvement were achieved. Resolution of submacular fluid, hemorrhage, or exudates was noted in six eyes; in the remaining eye there was persistence of subretinal lipid. There were no complications including optic neuropathy in any of the treated eyes. Follow-up ranged from 6 to 13.5 months following last treatment (mean, 10 months). CONCLUSION: Photodynamic therapy with verteporfin for extrafoveal symptomatic peripapillary CNV appears to be effective in improving vision and promoting the resolution of subfoveal exudates, hemorrhage, or fluid. A randomized controlled study with longer follow-up is justified.

Adult↗

Serious ophthalmic pathology compromising vision in HCV/HIV co-infected patients treated with peginterferon alpha-2b and ribavirin.

OBJECTIVE: To characterize the ocular changes associated with peginterferon alpha 2b (peg-IFN alpha-2b) and ribavirin therapy for chronic hepatitis C infection in HIV co-infected individuals. METHODS: A prospective, open-label trial treating HIV/hepatitis C (HCV) co-infected individuals with peg-IFN alpha-2b and ribavirin at the Warren Grant Magnusson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Twenty-three patients with a high mean CD4+ T-cell count were treated with peg-IFN alpha-2b and ribavirin and followed for 40 to 88 weeks. Ophthalmologic evaluations including visual acuity, visual field testing, color vision examination and indirect ophthalmoscopy were performed at baseline and every 3 months. RESULTS: Eight of the 23 patients (35%) developed ophthalmologic pathology, including cotton wool spots, cataracts, and two patients developed decreased color vision. These two patients regained their color vision, one after cessation of anti-HCV therapy. CONCLUSIONS: Although retinal pathologies have been reported in patients treated with interferon-alpha, they have not been reported during peg-IFN alpha-2b therapy nor in HIV/HCV co-infected patients. The incidence of serious ocular pathology associated with anti-HCV therapy may be very high and is probably associated with peg-IFN alpha-2b. Increased monitoring of patients treated with peg-IFN alpha-2b for retinal and visual changes is warranted.

Adult↗

Choroidal neovascularization in black patients.

OBJECTIVE: To characterize choroidal neovascularization (CNV) in black patients examined at a retinal disease referral center. DESIGN: Retrospective review of the medical records of all patients diagnosed as having CNV to identify black patients with CNV. SETTING: Single tertiary retinal referral center that included four ophthalmologists. PATIENTS: All patients diagnosed as having CNV between April 1990 and October 1992. MAIN OUTCOME MEASURES: Prevalence, demographic information, fundus photographic and fluorescein angiographic characteristics, natural history, and response to laser photocoagulation of CNV in black patients. RESULTS: Black patients comprise 15% of all patients seen at this center. Of 1725 patients identified as having CNV who were seen at the center during a 2.5-year period, only 25 were black (1.4%). In these patients, CNV was associated with a variety of retinal diseases, the most frequent being age-related macular degeneration. The average age of the study group was 54 years, women outnumbered men 2:1, and 13 of the patients developed bilateral lesions. Twelve of the 38 lesions were extrafoveal on presentation, and five of these were peripapillary. In the laser-treated eyes, recurrence of CNV was frequent and associated with visual loss. CONCLUSIONS: Choroidal neovascularization seems to be rare in blacks among a retinal disease referral center population. The overall presentation, natural history, and response to laser treatment seems to be similar to that of white patients. No feature of CNV in black patients was identified that would suggest that results of randomized clinical trials of laser photocoagulation for CNV are not valid for these patients.

Baltimore↗

Tricuspid valve group B streptococcal endocarditis after an elective termination of pregnancy.

A patient developed fever, chills, and shortness of breath after an elective first trimester dilation and curettage. Blood cultures grew Group B streptococcus, and a transesophageal echocardiogram revealed a 2 x 2 cm vegetation on the tricuspid valve and global left ventricular hypokinesis. A 6-week course of parenteral antibiotics and vasodilator therapy resulted in resolution of the valvular vegetation as well as of the left ventricular dysfunction.

Abortion, Therapeutic↗

Dye incorporation to enhance the laser ablation of standard and reduced-modulus bone cements.

Laser ablation of acrylic bone cement is an alternative method of cement removal that can be used during revision arthroplasty of cemented implants. This study investigated the feasibility of using a continuous-wave Argon ion laser (wavelength = 514 nm) with the addition of methylene blue or red dye no. 13 to enhance the ablation of two types of bone cements: polymethylmethacrylate and polybutylmethylmethacrylate. Six cement/dye combinations were studied while power (0.5, 0.75, and 1.0 W) and exposure times (30, 45, 60, and 90 seconds) were varied. The Argon laser was unable to ablate undyed polymethylmethacrylate or polybutylmethylmethacrylate. However, ablation was shown for both cements with either dye. The red dye had a stronger absorption peak at 514 nm than did the blue dye. Statistically larger ablation areas were seen for red polymethylmethacrylate than for blue polymethylmethacrylate (p < 0.013) at all levels tested. Ablation areas were larger in red than in blue polybutylmethylmethacrylate cement. Blue polybutylmethylmethacrylate cement produced larger ablation areas than did blue polymethylmethacrylate cements at all energy levels tested, with smaller surrounding damage areas. Red polybutylmethylmethacrylate cement also produced larger ablation areas than did red polymethylmethacrylate cement (at 0.75 and 1.0 W), again with smaller damage areas. Damage zones were smallest in red polybutylmethylmethacrylate cements at all test levels. These results suggest that, by using dyes to selectively alter the absorption characteristics of bone cement, laser ablation can be an effective method for cement removal. Changes in the chemical structure of the cement can also influence the response to laser treatment. Furthermore, the absorption spectra of the bone cement can be altered to maximize energy absorption at a wavelength that is not absorbed by bone tissue; this potentially minimizes damage to bone during revision surgery.

Arthroplasty↗

Clinical and histological evaluation of portwine stain treatment with a microsecond-pulsed dye-laser at 577 NM.

Test treatment of portwine stains (PWS) was performed with a microsecond-pulsed dye laser at 577 nm using a 2-mm spot diameter. Although selective coagulation of the erythrocytes occurred, this did not result in bleaching of the treated area. Massive destruction of the dilated capillaries is suggested to be a prerequisite for PWS-bleaching, very probably requiring msec (instead of microseconds) laser pulses.

Coloring Agents↗

Effect of pulse duration on microsecond-domain laser lithotripsy.

The pulsed dye laser (wavelength 504 nm, pulse duration 1 microsecond) is widely used for fragmenting urinary and biliary calculi. In this study, the performance of this laser was compared with pulsed dye lasers producing pulse durations of 8 and 20 microseconds. Fragmentation thresholds and fragmentation rates were measured using a variety of urinary and biliary calculi. Effective fragmentation of urinary and biliary calculi was obtained with 1-microsecond and 8-microseconds pulse durations, but satisfactory fragmentation could not be achieved at 20 microseconds.

Cholelithiasis↗