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S H Selman

Publications and source records attributed to S H Selman.

At least 19 recordsLinked to original sources

A new technique for bladder washing.

We describe a simple adaptation of the Water Pik (Teledyne Water Pik, Fort Collins, Colorado) irrigating device which allows vigorous, direct-vision agitation of the bladder wall. Three groups of mongrel dogs were subjected to cystoscopy and either syringe barbotage, half-speed Water Pik irrigation, or full-speed Water Pik irrigation of the bladder wall. Transitional cell counts were then done on centrifuged aliquots of each bladder wash specimen. The average number of transitional cells per high-power field were similar between the control group and the syringe barbotage group (2.5 and 1.5 respectively). However, both the half-speed and the full-speed Water Pik groups demonstrated statistically higher cell counts (5.7 and 13.7) when compared to both the controls and syringe barbotage groups. We conclude that Water Pik irrigation is an effective method to increase cell yield in bladder wash specimens.

Animals

Mechanisms of cell killing in photodynamic therapy using a novel in vivo drug/in vitro light culture system.

Photodynamic therapy of certain neoplasms has emerged as a promising form of cancer treatment. This type of therapy involves the exogenous administration of a photosensitizer with subsequent exposure to light. The ensuing photochemical reaction results in destruction of the tumor. Whether tumor cells are destroyed directly by the photodynamic treatment or indirectly as a result of destruction of the tumor microvascular bed is unknown. To address this question, methods were adapted to test whether combinations of a photosensitizer and light resulted in direct cell killing of precision cut tissue slices placed in culture. The major advantages of this culture system are that photosensitizers are administered in vivo, tissue slices produced in minutes, placed in culture medium, and irradiated in vitro. Any resulting cellular destruction occurs in the absence of a functioning vascular system and indicates that photodynamic therapy acts through a direct cell killing mechanism. Tissue slice viability was monitored by two standard methods: assay for intracellular potassium and morphological examination at the electron microscopic level. The effects of hematoporphyrin derivative and light were examined on tissue slices produced from a prostate adenocarcinoma transplanted into male Copenhagen rats. The data indicate that direct killing of tumor slices occurs and is dependent on the irradiation protocol used.

Animals

Observations on the synthesis and in vivo photodynamic activity of some benzochlorins.

An improved synthesis of benzochlorins is reported. Demetallation of the meso-hydroxymethylvinyl derivative of octaethylporphyrin, followed by treatment with sulfuric acid results in cyclization to generate the corresponding octaethylbenzochlorin in high yield. Prolonged treatment with acid generates the sulfonated derivative. These sensitizers were shown to be efficient photodynamic agents in vivo. Animals bearing a transplanted N-[4-(5-nitro-2-furyl)-2-thiazoly]formamide induced urothelial tumor were treated with either the benzochlorin or its sulfonated derivative. Irradiation of tumors 24 h later resulted in a significant tumoricidal effect in a short term assay. We conclude that benzochlorins warrant further examination as potential agents for use in photodynamic therapy.

Animals

Synthesis and in vivo photodynamic activity of some bacteriochlorin derivatives against bladder tumors in rodents.

Bacteriochlorins have been suggested as potential photosensitizers for use in photodynamic therapy. We have shown that bacteriochlorin-like macrocycles can be generated through cyclization of either 5,10- or 5,15-bis[(ethoxycarbonyl)vinyl]porphyrins; however, the resulting products are rapidly decomposed on exposure to air. More stable systems can be generated by Diels-Alder reactions between dienophiles such as dimethyl acetylenedicarboxylate or tetracyanoethylene, and vinylporphyrinones. Although spectroscopic properties of these latter products resemble those of porphyrinones rather than bacteriochlorins, in vivo studies using the N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced rat bladder tumor (AY-27) transplanted into Fisher CDF (F344)/CrlBr rats demonstrated a powerful photodynamic response.

Animals

Photodynamic therapy: effect on the endothelial cell of the rat aorta.

Previous studies in our laboratory have demonstrated that photodynamic therapy (PDT) of experimental bladder tumors leads to rapid destruction of the endothelial lining within the tumor microvasculature. Endothelial cell death during PDT may be a consequence of direct cell injury resulting from retention of photosensitizer within the endothelial cell or, alternatively, result from intravascular activation of circulating photosensitizer with subsequent indirect endothelial damage. In the experiments described here, we investigated the possibility that photosensitizer retained within the endothelial cell was sufficient to cause endothelial cell injury in the absence of circulating drug. The experimental model was rat aorta photosensitized in vivo via the intravenous injection of tin(II) etiopurpurin dichloride (SnET2), and subsequent in situ or in vitro (in explant culture) light (670 nm) treatment from an argon pumped dye laser. Damage to the lining of the aorta was assessed morphometrically by determining the areal density of silver stained endothelial cells. Results indicate that purpurin SnET2-PDT directly damages the endothelial lining.

Animals

Hemodynamic effect of the metallopurpurin SnET2 and light on transplantable FANFT induced bladder tumor.

Changes in blood flow to transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide induced bladder tumors growing subcutaneously in the flanks of Fischer CDF (F344/CrlBR) rats were measured after photodynamic therapy with the photosensitizer tin (II) etiopurpurin dichloride using the radioactive microsphere technique. As with the other photosensitizers, hematoporphyrin derivative and chloroaluminum tetrasulfophtalocyanine, tin (II) etiopurpurin dichloride and light caused a rapid decrease in tumor blood flow in this tumor model. The decrease in blood flow occurred whether the vehicle for photosensitizer delivery was an emulsion or a liposome. Systemic heparinization of animals prior to light treatment did not alter changes in tumor blood flow.

Animals

Diels-Alder adducts of vinyl porphyrins: synthesis and in vivo photodynamic effect against a rat bladder tumor.

Benzoporphyrin derivatives have been proposed as potential photosensitizers for photodynamic therapy. We have prepared a number of benzoporphyrin derivatives and tested their effect, in combination with red light, on the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) induced rat bladder tumor (AY-27) transplanted into Fischer CDF(F344)/CrlBr rats. Tetracyanoethylene (TCNE) adducts showed very little activity, which may be attributable to their poor tumor uptake or to chemical instability of the adduct under physiological conditions. However, dimethyl acetylenedicarboxylate (DMAD) adducts tested showed greater cytotoxic effect than hematoporphyrin derivative and similar activities to metallopurpurins when tested under the same protocol.

Acetylene

Metallopurpurins and light: effect on transplantable rat bladder tumors and murine skin.

Purpurins are modified chlorins with photodynamic properties. Their strong absorption in the red region of the visible spectrum makes them candidates for use in photodynamic cancer therapy. A series of metal derivatives of the free base purpurins have been synthesized and shown to cause tumor necrosis in transplantable tumors when exposed to visible light. In the following set of experiments, the effects of two metallo-derivatives (tin and zinc) of two purpurins, octaethylpurpurin (NT2) and etiopurpurin (ET2), and light on the N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide transplantable tumors in Fischer CDF(F344)/CrlBr rats were studied. The photodynamic activity was assessed by a short term assay using tumor dry weight 12 days after purpurin-PDT as a criterion of response. From these experiments it appears that SnET2 greater than SnNT2 greater than ZnET2 greater than ZnNT2 in photodynamic activity. SnET2 was further characterized by attempting to determine the time interval after systemic injection at which maximum therapeutic effect occurred. These studies shown that 24 h after metallopurpurin injection was the optimum time for treatment of tumors with visible light. In a final set of experiments, the effect of solar light on the skin of hairless mice injected with SnET2 was found to be much less injurious than with hematoporphyrin derivative.

Animals

Cyclosporine versus azathioprine: a review of 200 consecutive cadaver renal transplant recipients.

Most renal transplant centers report an increase in graft survival when cyclosporine is used as a primary immunosuppressant. We report the outcome of 200 consecutive cadaver renal transplant recipients among whom initial immunosuppression and risk factors were similar except for the substitution of cyclosporine for azathioprine in the second 100 recipients. Azathioprine-treated recipients had significantly increased (p less than 0.05) mean hospital stays (31.9 versus 18.3 days), incidence of first rejection episodes (85 versus 31) and methylprednisolone dose (3.38 versus 0.06 gm. per patient). Cyclosporine-treated recipients had a significantly higher 1-year mean serum creatinine level (1.85 versus 1.56 mg. per dl.) and 1-year actual graft survival (83 versus 58 per cent). Despite mild nephrotoxicity, cyclosporine is superior to azathioprine as a primary immunosuppressant in cadaver kidney transplantation.

Azathioprine

New sensitizers for photodynamic therapy: controlled synthesis of purpurins and their effect on normal tissue.

Purpurins are a class of porphyrin derivative that have been shown to have good in vivo cytotoxicity to N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) induced rat bladder tumors (AY-27) implanted into Fisher 344 rats. The synthesis of purpurins from etioporphyrin I and coproporphyrin I proceeds in high yield and with a high degree of regioselectivity. Product formation can be rationalized in terms of relief of steric strain about the periphery of the purpurin macrocycle. The effect of therapeutic light doses using the rat footpad model suggests that, at therapeutic sensitizer doses, normal tissue damage is within acceptable limits, particularly for metalated purpurins.

Animals

Genitourinary malignancies.

Malignancies of the male genitourinary system make up a significant proportion of current urologic practice. The primary physician plays an important role in the early detection and referral of patients with these problems. Early treatment offers the best chance of disease control. It is encouraging that some of the most dramatic strides in the treatment of solid tumors have been made in the field of urologic oncology. It is anticipated that the coming years will continue to witness advancement in the treatment of urologic malignancies.

Humans

New photosensitizers for photodynamic therapy: combined effect of metallopurpurin derivatives and light on transplantable bladder tumors.

A series of metallopurpurins was tested for their photodynamic activity against transplantable N-[4-(5-nitro-2-furyl)-2-thiazoyl]formamide-induced urothelial tumors growing in male Fischer CDF (F344/CrlBR) rats. Histological examination of tumors in animals treated with the metallopurpurins and red light (greater than 590 nm, 360 J/cm2) revealed tumor necrosis 24 h after completion of therapy. Control tumors showed no histological change. In 30-day tumor regrowth studies, 70% of animals treated with the metallopurpurin derivative SnET2 were free of tumors while 50% of the animals treated with the free-base purpurin ET2 were free of tumor. Metallopurpurins have intense absorptions in the red region of the visible spectrum, a region with good tissue penetration. The metallopurpurins are easily prepared from the corresponding purpurins with a high degree of purity. This study demonstrates the potential of these photosensitizers for photodynamic cancer therapy.

Animals

Morphological study of the combined effect of purpurin derivatives and light on transplantable rat bladder tumors.

Purpurin derivatives, a group of synthetic photosensitizers, were tested for their photodynamic activity against transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced urothelial tumors growing in male Fischer 344 rats. Histological examination of tumors in animals treated with the purpurin derivatives and red light (greater than 590 nm, 360 joules/cm2) revealed tumor cell necrosis 24 h after completion of therapy. Control tumors showed no histological change. Purpurins have a major absorption peak in the red region (greater than 650 nm) of the visible spectrum, a region with good tissue penetration, and purpurins can be synthesized with a high degree of purity. This study demonstrates the potential of purpurin derivatives as photosensitizers for photodynamic cancer therapy.

Animals

Small bilateral renal cell carcinomas.

A case of multicentric bilateral small renal cell carcinomas is presented. The two largest tumors were detected by computerized tomography (CT) and the diagnosis confirmed by ultrasound and fine needle biopsy.

Biopsy

A dose response analysis of purpurin derivatives used as photosensitizers for the photodynamic treatment of transplantable FANFT induced urothelial tumors.

Rats engrafted with transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced urothelial tumors were treated with purpurin derivatives and red light (greater than 590 nm., 360 joules/cm.2). Treated and control tumors were harvested 12 days after treatment and dry weights compared. At doses of 5.0 micrograms./gm. and 2.5 micrograms./gm. body weight, the purpurins designated NT1 and NT2, when combined with light, caused statistically significant (p less than 0.02) tumor regression when compared to light shielded controls. At 1.0 micrograms./gm. body weight, NT1 and light also induced significant tumor regression (p less than 0.02). Purpurins, which have strong absorption bands above 650 nm. and can be synthesized with a high degree of purity, appear to have potential as photosensitizers for photodynamic therapy.

Animals