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Biomedical subjects

R R Anderson

Publications and source records attributed to R R Anderson.

At least 73 records · Page 4Linked to original sources

Skin necrosis due to photodynamic action of benzoporphyrin depends on circulating rather than tissue drug levels: implications for control of photodynamic therapy.

In an ideal world, photodynamic therapy (PDT) of abnormal tissue would reliably spare the surrounding normal tissue. Normal tissue responses set the limits for light and drug dosimetry. The threshold fluence for necrosis (TFN) was measured in normal skin following intravenous infusion with a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA) Verteporin as a function of drug dose (0.25-2.0 mg/kg), wavelength of irradiation (458 and 690 nm) and time interval (0-5 h) between drug administration and irradiation. The BPD-MA levels were measured in plasma and skin tissue to elucidate the relationship between TFN, drug kinetics and biodistribution. The PDT response of normal skin was highly reproducible. The TFN for 458 and 690 nm wavelengths was nearly identical and the estimated quantum efficiency for skin response was equal at these two wavelengths. Skin phototoxicity, quantified in terms of 1/TFN, closely correlated with the plasma pharmacokinetics rather than the tissue pharmacokinetics and was quadratically dependent on the plasma drug concentration regardless of the administered drug dose or time interval between drug and light exposure. This study strongly suggests that noninvasive measurements of the circulating drug level at the time of light treatment will be important for setting optimal light dosimetry for PDT with liposomal BPD-MA, a vascular photosensitizer.

Animals↗

Effects of heterogeneous absorption of laser radiation in biotissue ablation: characterization of ablation of fat with a pulsed CO2 laser.

BACKGROUND AND OBJECTIVE: Physicians encounter several clinical situations in which fat must be removed. In this study, the characterization of fat ablation produced by a pulsed CO2 laser is reported. STUDY DESIGN/MATERIALS AND METHODS: An RF excited 800 microns pulsed CO2 laser operating at 10.6 microns was used to ablate fresh porcine fat. The heat of ablation and ablation threshold were determined using a mass loss technique. Absorption coefficients for fat and dermis were determined by attenuated total reflection spectroscopy. RESULTS: Threshold radiant exposure and heat of ablation for fat were calculated from the mass loss measurements to be 1.05 J/cm2 and 2.4 J/cm3, respectively. The absorption coefficients of fat and dermis at 10.6 microns were 250 and 780 cm-1, respectively. Pulsed CO2 laser ablation of fat caused ejection of fat droplets, which ignited after high fluence pulses. CONCLUSION: A pulsed CO2 laser can effectively ablate fat with a threshold fluence and efficiency comparable to other soft tissues. Our data suggest that fat ablation occurs primarily through the ejection of intact fat particles via the explosive vaporization of intervening water "lakes".

Adipose Tissue↗

Delayed hemolytic transfusion reaction due to anti-Js(a) in an alloimmunized patient with a sickle cell syndrome.

Delayed hemolytic transfusion reactions occur via an anamnestic immune response in patients previously alloimmunized by certain RBC antigens. Conventional pretransfusion antibody screening tests and crossmatches are unable to detect certain antibodies that potentially can cause these reactions because they may be present in low concentrations or have low affinity for their respective antigen or their indicator antigen may be absent from test RBCs. We report the second case of a delayed hemolytic transfusion reaction caused by an undetectable (by routine methods) anti-Js(a) in a patient with a sickle cell syndrome (hemoglobin SC disease) and multiple alloantibodies, in whom retrospective indirect antiglobulin tests enhanced by polyethylene glycol revealed the presence of weakly reactive anti-Js(a).

Female↗

Iontophoretic delivery of ALA provides a quantitative model for ALA pharmacokinetics and PpIX phototoxicity in human skin.

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) is increasingly employed for skin cancer, yet ALA dosing is crude. Using iontophoresis, we developed a rapid and quantifiable system for topical ALA delivery, with measurement of subsequent PpIX fluorescence and phototoxicity. ALA was iontophoresed from a 2% solution into upper inner arm skin of 13 healthy volunteers. Six doses of ALA were delivered with a series of charges varying from 3-120 milliCoulombs (mC); four additional doses were given with a charge of 60 mC. Five hours post-iontophoresis, sites were irradiated with broad-band yellow-red light, the series of six ALA doses receiving 100 J/cm2, while the four identical doses received 6.25, 12.5, 25, and 50 J/cm2, respectively. Resultant erythema was measured by reflectance spectroscopy. The time course of PpIX fluorescence was ALA-dose-dependent. With charge < or = 24 mC, PpIX fluorescence peaked at 3 h and returned to zero at 9-10 h, whereas charges > 24 mC had a sustained peak at 5-10 h, falling to zero by 24 h. Pre-irradiation, PpIX fluorescence correlated with ALA dose (r = 1.0). PpIX fluorescence fell immediately post-irradiation (p < 0.0001); recovery levels at 3 h correlated with ALA dose (p < 0.0001). Delayed erythema correlated with ALA dose and irradiation dose (p < 0.0001, p < 0.01, respectively). Both PpIX fluorescence intensity pre-irradiation and fall in PpIX fluorescence post-irradiation correlated with erythema (r = 0.98). Hence, PpIX synthesis is ALA-dose-dependent, and phototoxicity can be predicted from ALA dose, irradiation dose, and photobleaching of PpIX. This reproducible system allows accurate dosimetry in topical PDT and facilitates study of ALA metabolism.

Adult↗

Predictive dosimetry for threshold phototoxicity in photodynamic therapy on normal skin: red wavelengths produce more extensive damage than blue at equal threshold doses.

The goal of this investigation was to establish methodology to determine and prevent phototoxic responses of normal skin to photodynamic therapy (PDT). The drug used was a second-generation photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA). The dependence of skin phototoxicity on drug dose (0.5-2.0 mg/kg), fluence (1.2-390 J/cm2), and wavelength (690 nm and 458 nm) was studied in the New Zealand albino rabbit in the first 5 h after injection. Skin responses were recorded for 2 wk after irradiation. Noninvasive measurements of drug fluorescence were made on unexposed skin sites during the first 5 h after drug injection. Immediate responses to PDT included erythema induced by 458 nm light and blanching induced by 690 nm light. Delayed reactions included edema on the day of exposure, purpura at 24 h, eschar by day 2 or 3, and scar by the end of follow-up. The threshold fluence for immediate responses correlated strongly with the threshold fluence for delayed reactions. The induction of threshold purpura on day 1 was a reliable index for skin phototoxicity that led to necrosis. The minimum purpura dose on day 1 after irradiation increased exponentially with the interval between drug injection and irradiation, independent of irradiation wavelength, for all drug doses. The action spectrum for threshold purpura mimics closely the absorption spectrum of BPD-MA. The in vivo drug fluorescence correlated with skin phototoxicity, thus allowing predictive dosimetry. This model system defines the safety limits for skin phototoxicity of PDT with BPD-MA.

Animals↗

Recurrent CDC group IVc-2 bacteremia in a human with AIDS.

A 30-year-old man with AIDS developed separate episodes of bacteremia with multiple organisms including CDC group IVc-2, related to an indwelling central venous catheter. Recovery at each interval followed antibiotic therapy and replacement of the central venous access. This is the first reported case of infection with this organism in a patient with AIDS. A review of the biochemical features of this bacterium as well as pertinent literature is presented.

AIDS-Related Opportunistic Infections↗

DNA ploidy changes in rhino mouse skin induced by all-trans retinoic acid and retinol.

OBJECTIVE: In order to assess the proliferative changes induced by all-trans retinoic acid (RA) and retinol (ROL), we have carried out a study of the DNA content of basal and suprabasal keratinocytes after epicutaneous application on the rhino mouse. STUDY DESIGN: Skin sections were analyzed stereologically and cytophotometrically using the Feulgen technique. The diploid DNA value (2C) was obtained from hepatocyte nuclei of control animals. Whereas cells in phase G0-G1 will show a 2C content, cells during phase S and in phase G2-M will show DNA values ranging from 2C to 4C and 4C, respectively. RESULTS: Although epidermal thickness (ET) increased significantly in all treated animals, surface density only increased in animals treated with all-trans RA. Quantification of DNA content of basal keratinocytes showed reduction of 2C and 2C-4C populations with a commensurate increase in proportions of cells with 4C and > 4C in the animals treated with 0.025% all-trans RA and ROL. Suprabasal keratinocytes of mice treated with 0.025% all-trans showed a decrease of the 2C population and an increased proportion of cells with 4C. Whereas 0.025% all-trans RA induced an increase of both basal and suprabasal DNA indices, ROL enhanced only the basal DNA index significantly. CONCLUSION: Animals treated with 0.025% ROL showed a significant increase in the basal proliferative index (PI) while the suprabasal PI remained constant; treatment with 0.025% all-trans RA produced a significant increase of both basal and suprabasal PIs and parakeratotic hyperkeratosis probably due to incomplete differentiation.

Administration, Cutaneous↗

Photodynamic therapy of extracellular matrix stimulates endothelial cell growth by inactivation of matrix-associated transforming growth factor-beta.

Photodynamic therapy (PDT), the production of cytotoxic free-radical moieties by light activation of photosensitizer dyes, is a novel approach to inhibit experimental intimal hyperplasia. Local eradication of vascular cells with this method in vivo is followed by expedient reendothelialization, and PDT of extracellular matrix (ECM) in vitro stimulates endothelial cell (EC) growth. This in vitro study explored one possible mechanism underlying these findings by investigating the effects of PDT on matrix-associated transforming growth factor-beta (TGF-beta), a potent inhibitor of EC growth. The ECM deposited by EC on tissue culture plates contained 85.4 +/- 10.2 pg/10 cm2 of TGF-beta, as measured by an ELISA. In contrast, after PDT of ECM, levels of TGF-beta could be barely be detected (0.2 +/- 0.5 pg/10 cm2). The functional consequence of this observation was demonstrated by the finding that PD1 of plates coated with a fibronectin-TGF-beta complex stimulated EC mitogenesis (102.3% +/- 19.3%, p < 0.0005) compared with the untreated control (44.1% +/- 13.5%). The inhibitory effect of ECM-associated TGF-beta on EC was further delineated by blocking its activity with a specific antibody. Whereas the antibody did not affect EC mitogenesis or PDT-treated matrix or matrix-free plates (101% +/- 8.8%, 105.6% +/- 9.8%), EC mitogenesis growing on ECM was significantly enhanced (125.9%, 17.5%, p < 0.05). Finally, SDS-PAGE analysis of PDT-treated TGF-beta in solution demonstrated that the PDT-mediated loss of TGF-beta activity was not associated with changes in its molecular weight. These data demonstrate that increased EC proliferation on PDT-treated matrix is, at least in part, mediated by inactivation of TGF-beta. PDT-removal of this EC growth inhibitor in the intima provides a mechanism by which PDT of the vascular wall could potentiate endothelial regrowth, a factor which may promote proper healing and result in the inhibition of intimal hyperplasia.

Animals↗

Clinical and histological responses of congenital melanocytic nevi after single treatment with Q-switched lasers.

BACKGROUND: Laser irradiation of congenital melanocytic nevi is a controversial treatment. Recurrence of lesions after laser treatment appears to be the rule, and the effects of laser irradiation on cellular biological behavior and the possible mutagenic responses of nevomelanocytes that have received nonlethal doses of irradiation are still unclear. Without treatment, there is an increased potential for malignant degeneration over a life-time. The purpose of this study was to examine the effects of Q-switched lasers on congenital nevi and to explain the mechanism(s) behind the response of the nevi to laser treatment. Five congenital nevi were divided into 3 equal parts: 1 part was treated with the Q-switched ruby laser at a wavelength of 694 nm, 1 part was treated with the Q-switched neodymium: YAG laser at a wavelength of 1064 nm, and 1 part was left untreated to serve as control. At intervals ranging from 3 days to 3 months after laser irradiation, the lesions were excised and evaluated by routine staining. This clinical study was conducted entirely at the Massachusetts General Hospital Dermatology Laser Center, Boston, Mass. OBSERVATIONS: Both the superficial and the deep portions of the congenital melanocytic nevi were affected by the 2 lasers, as evidenced by macroscopic inspection as well as microscopic evaluation. However, the Q-switched laser treatment did not destroy all nevomelanocytes, particularly in the deeper, less pigmented portions of the lesions. CONCLUSIONS: Both the Q-switched ruby laser and the neodymium: YAG laser often removed only the superficial portion of the congenital melanocytic nevi. The Q-switched ruby laser (694 nm) appeared to be more effective in removing nevomelanocytes than the Q-switched neodymium: YAG laser (1064 nm).

Adolescent↗

Risks of transfusion and organ and tissue transplantation: practical concerns that drive practical policies.

The risks and other adverse effects associated with blood transfusion and tissue and organ transplantation were reviewed retrospectively with the use of recent US activity data and published compilations of such events for both therapeutic modalities. In addition, practices that govern blood transfusion and transplantation, in light of regulations and standards of practice, and the practical factors that cause variations in the use of both therapies were compared and contrasted. These factors include availability, preservation and viability, life-saving vs life-enhancing effects, donor selection and qualification, donor-recipient pair matching, disease marker screening and transmission potential, immunopathologic considerations, and future alternative directions.

Communicable Diseases↗

Selectivity of protoporphyrin IX fluorescence for condylomata after topical application of 5-aminolaevulinic acid: implications for photodynamic treatment.

To examine the potential of using photodynamic therapy (PDT) in condylomata, we studied the distribution and kinetics of protoporphyrin IX (PpIX) formation in condylomata acuminata and adjacent normal skin after topical application of 5-aminolaevulinic acid (ALA). PpIX fluorescence spectra were measured hourly in vivo after ALA application. After gross fluorescence imaging, the lesions were biopsied, and fluorescence microscopy was performed. All three PpIX fluorescence detection modalities suggested selectivity of PpIX formation in condylomata after topical ALA application. In 17 of 25 condylomata, there was significantly greater fluorescence compared with adjacent normal skin. The greatest lesional to normal skin fluorescence ratios occurred after 2 h. The most likely mechanism for increased lesional PpIX formation in condylomata is enhanced stratum corneum permeability. Based on our results, ALA/PDT is a potential field therapy for condylomata. PpIX fluorescence imaging after ALA application may also be useful for localizing condylomata prior to treatment.

Administration, Cutaneous↗

Effects of CO2 laser pulse duration in ablation and residual thermal damage: implications for skin resurfacing.

BACKGROUND AND OBJECTIVES: Resurfacing with the CO2 laser is rapidly gaining acceptance for skin rejuvenation. Advances in CO2 laser and scanning technology allow for precise tissue removal with minimal thermal damage. High energy CO2 laser pulses have been widely used effectively to smooth the surface of facial skin; however, pulse duration effects on ablation and thermal damage have not been systematically studied over the milli-second region (0.25-10 ms). STUDY DESIGN/MATERIALS AND METHODS: This study characterizes the ablation threshold, heat of ablation, and residual thermal damage in skin resulting from CO2 laser pulses with a Gaussian beam profile. Mass loss from fresh pig skin was measured with an analytical balance, and residual thermal damage was determined through histology. RESULTS: Pulse durations > 1 ms were associated with higher ablation thresholds and localized increased thermal damage. CONCLUSIONS: Our results show that although pulse duration is an important determinant in ablation and thermal damage, irradiance is more critical as an independent parameter in predicting the effects of CO2 laser pulses.

Animals↗

Drosophila melanogaster larvae detect low doses of UVC radiation as manifested by a writhing response.

Exposure of insects and higher orders of animals to UVC radiation has been shown to result in toxicity with a delayed expression. We have observed an immediate writhing response in slowly wandering third instar larvae of Drosophila melanogaster exposed to UVC radiation at doses that were not lethal. UVB and UVA radiation had no effect. Mutants for the visual and sensory systems appeared to respond normally, but CO(2) anesthesia resulted in reversible inhibition. ebony and silver mutants, which affect different pathways in catecholamine metabolism, showed an absent to reduced response. Using UVC lasers, we were able to demonstrate a response in different regions of the larval body. Furthermore, a 193 nm laser that penetrates only 2-5 micron(s) was able to induce a response but unable to kill the larvae. These results suggest a photochemical reaction occurs in the cuticle which produces free radicals that stimulate the nerves and muscle which are present immediately below the epidermis. Possible targets for the UVC radiation are catecholic compounds secreted and processed into the cuticle of third instar larvae just to pupariation whose primary function is to crosslink the protein and carbohydrate components.

Animals↗

Laser treatment of tattoos in darkly pigmented patients: efficacy and side effects.

BACKGROUND: Many modalities for the treatment of tattoos and pigmented lesions produce a greater risk of complications in Fitzpatrick types V and VI skin because of an increased incidence of adverse pigmentary changes and keloidal scarring. In fair-skinned persons Q-switched lasers have proved effective in removing pigmented lesions and tattoos without scarring. OBJECTIVE: This study was conducted to determine the efficacy and effects of Q-switched lasers on a small series of darkly pigmented patients with tattoos. METHODS: Four patients of Ethiopian origin with facial and neck tribal tattoos were treated with both the Q-switched ruby and Nd:YAG lasers. One black woman with a multicolored tattoo on the mid chest was treated with the Q-switched ruby laser. RESULTS: Clearing of all lesions was seen. The treatments did not result in scarring or permanent pigment changes other than the ones intended. CONCLUSION: Our results indicate that in darkly pigmented patients, Q-switched laser treatment of tattoos can be performed successfully. The longer wavelength Q-switched Nd:YAG laser is recommended when removing tattoos in darker complected persons. A test treatment is advised before treatment of large skin areas.

Adult↗

Damage to hair follicles by normal-mode ruby laser pulses.

BACKGROUND: Although many temporary treatments exist for hirsutism and hypertrichosis, a practical and permanent hair removal treatment is needed. OBJECTIVE: Our purpose was to study the use of normal-mode ruby laser pulses (694 nm, 270 microseconds, 6 mm beam diameter) for hair follicle destruction by selective photothermolysis. METHODS: Histologically assessed damage in ex vivo black-haired dog skin after the use of different laser fluences was used to design a human study; 13 volunteers with brown or black hair were exposed to normal-mode ruby laser pulses at fluences of 30 to 60 J/cm2, delivered to both shaved and wax-epilated skin sites. An optical delivery device designed to maximize light delivery to the reticular dermis was used. Hair regrowth was assessed at 1, 3, and 6 months after exposure by counting terminal hairs. RESULTS: Fluence-dependent selective thermal injury to follicles was observed histologically. There was a significant delay in hair growth in all subjects at all laser-treated sites compared with the unexposed shaven and epilated control sites. At 6 months, there was significant hair loss only in the areas shaved before treatment at the highest fluence. At 6 months, four subjects had less than 50% regrowth, two of whom showed no change between 3 and 6 months. Transient pigmentary changes were observed; there was no scarring. CONCLUSION: Selective photothermolysis of hair follicles with the normal-mode ruby laser produces a growth delay consistent with induction of prolonged telogen with apparently permanent hair removal in some cases.

Animals↗

Triiodothyronine-induced hyperthyroidism and reproduction in female rats.

The effect of L-triiodothyronine (L-T3)-induced hyperthyroidism on reproduction in female rats was studied. Treatment groups used were normal control, 1, 2, 4, 8, and 16 micrograms L-T3/100 g body weight (b.w.)/day. Subcutaneous injections of L-T3 began the first day of estrus until day 1 or day 19 of lactation. All rats given 1, 2, or 4 micrograms L-T3 had regular estrous cycles and normal number of pregnancies. Levels of L-T3 at 8 or 16 micrograms results in abnormal estrous cycles. Only one pregnancy occurred in the 8 micrograms group and no rats became pregnant in the 16 micrograms group. While groups on 1 or 2 micrograms L-T3 had normal parturition, groups on 4 micrograms or more showed signs of dystocia. Only the 1 microgram L-T3 group lactated to day 20, but at 67% of normal control. All levels above 1 micrograms showed loss of pups by day 2 of lactation due to lack of milk production, loss of maternal behavior, and cannibalism. Mammary gland wet and dried fat-free tissue (DFFT) weights were decreased in all treated groups except 1 microgram L-T3. The wet and DFFT weights of thyroids and uteri on days 2 or 20 of lactation were not altered by L-T3 treatment, but levels above 1 microgram increased both wet and DFFT weights of adrenal glands and ovaries. The data indicate that the no observed adverse effect level (NOAEL) of L-T3 for female rat reproduction would be below 1 microgram/100 g b.w./day. L-T3 treatment at 1 microgram/100 b.w./day or above is detrimental. These effects may be mediated through a hormonal imbalance due to the accelerated metabolic rate in reproductive tissues associated with hyperthyroidism.

Adrenal Glands↗

Monitoring of Culicoides spp. at a site enzootic for hemorrhagic disease in white-tailed deer in Georgia, USA.

Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) were monitored at a Georgia (USA) site where epizootic hemorrhagic disease (EHD) and bluetongue (BT) viruses are enzootic among white-tailed deer (Odocoileus virginianus). Collections were made using a captive white-tailed deer and light traps from June 1993 through November 1994. We collected 210,482 females from the captive deer during morning and evening periods. Predominant species were C. lahillei (73%), C. stellifer (16%), C. biguttatus (6%), C. niger (3%), C. spinosus (2%), and C. paraensis (0.2%). Other species were C. venustus, C. obsoletus/sanguisuga, C. haematopotus, C. guttipennis, and C. arboricola, which together represented < 0.1% of the specimens collected. No C. variipennis, a known vector of EHD and BT viruses, were collected from the deer. An estimated 953,299 females were collected in 695 light-trap nights. The most common species in light-trap collections were C. spinosus (45%), C. biguttatus (27%) and C. stellifer (24%). Culicoides variipennis was rare in the light-trap samples, representing < 0.01% of the total collections. There was serological evidence from hunter-killed deer that local deer were infected with EHD and BT viruses during the study, particularly during 1994. A primary suspect vector was C. lahillei, which attacked the bait deer in large numbers during the summer and early fall of both 1993 and 1994. Based on their seasonality, relative abundance, and host-seeking activity, C. stellifer and C. spinosus also were considered as possible vectors. However, virus isolation attempts on 113,716 Culicoides, including 62,530 C. lahillei and 32,769 C. stellifer, were negative.

Animals↗