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Biomedical subjects

M W Reed

Publications and source records attributed to M W Reed.

At least 109 records · Page 6Linked to original sources
PubMed1990

The association between thyroid neoplasia and intestinal polyps.

Recent reports have suggested an association between familial adenomatous polyposis and papillary carcinoma of the thyroid. This report describes four patients, each with intestinal polyps and thyroid or thyroglossal cyst carcinoma. One patient had a medullary rather than papillary carcinoma of the thyroid and in another the intestinal polyps were due to Peutz-Jeghers syndrome. This may indicate a wider association between thyroid carcinoma and intestinal polyps than has previously been recognised.

Adult↗
PubMed1989

Wide local excision as the sole primary treatment in elderly patients with carcinoma of the breast.

Clinically localized carcinoma of the breast in 96 women was treated by wide local excision alone. The locoregional recurrence rate was 35 per cent at a mean follow-up of 47 months. There was no significant effect of recurrence on survival because of the relatively high mortality rate from unrelated conditions in these mainly elderly patients. Recurrence was successfully managed with tamoxifen in the majority of cases, with few patients requiring radiotherapy or further surgery. Recurrence in the breast was associated with significantly less systemic disease and mortality than recurrence in the axilla.

Aged↗
PubMed1989

The rat urinary bladder: vasoactivity and macromolecular leakage in a new model.

An in vivo model of the rat urinary bladder microcirculation has been developed and microcirculatory responses to agents which produce vasoconstriction, vasodilation, and macromolecular leakage have been characterized. The urinary bladder of anesthetized female Sprague-Dawley rats is exteriorized and positioned in a tissue bath with a single stay suture which does not penetrate the lumen of the bladder. All blood vessels and nerves from the animal remain intact. The tissue bath is filled with Krebs solution which is monitored and maintained at a temperature of 36 +/- 0.5 degrees and a pH of 7.4 +/- 0.5. In vivo television microscopy is used to monitor vascular diameter and flow changes and isothiocyanate-tagged bovine serum albumin fluorescence is used as an index of macromolecular leakage. Norepinephrine (10(-6) M) caused a statistically significant decrease in vascular diameters of both arterioles and venules while sodium nitroprusside (10(-7) M) significantly increased arteriolar and venular diameters, histamine (10(-4) M) caused no change in venular diameters but did induce a significant macromolecular leak from those vessels. Compound 48/80 (1 and 10 micrograms/ml) induced a significant dose-dependent macromolecular leakage from venules. However, only with the 10 micrograms/ml dose was there visually detectable mast cell degranulation. It is concluded that this rat urinary bladder model provides a stable, reproducible model of a smooth muscle microcirculatory bed in a controlled environment, which responds similarly to other microcirculations.

Animals↗
PubMed1989

The response of the rat urinary bladder microcirculation to photodynamic therapy.

Light activation of dihematoporphyrin ether (photofrin II) has been used in the treatment of bladder tumors, yet the effects of this treatment on the normal urinary bladder microcirculation have not been determined. This study involved the use of in vivo television microscopy to observe the effects of light activation (530 to 560 nm., 175 mW/cm.) on the urinary bladder microcirculation of female Sprague-Dawley rats. Animals pretreated with dihematoporphyrin ether 30 minutes prior to light activation had high serum and low tissue concentrations of the photosensitizer and activation resulted in a statistically significant reduction of red blood cell column diameter in both arterioles and venules. The reduction was primarily due to mural thrombus formation with the occlusion remaining 60 minutes after activation. Animals pretreated 48 hours before activation had low serum and high tissue concentrations of dihematoporphyrin ether and activation had no microcirculatory effects apart from occasional platelet aggregation. These results suggest that the photodynamic effect on normal (non-neoplastic) tissue treated more than 48 hours after administration of dihematoporphyrin ether is probably due to a direct effect of light and the sensitizer on the smooth muscle of the bladder rather than an effect on the microcirculation.

Animals↗
PubMed1989

The microvascular effects of photodynamic therapy: evidence for a possible role of cyclooxygenase products.

Photodynamic therapy (PDT) of malignant tumours may involve the interruption of tumor and peritumor microcirculation. We have studied the effect of light activation of the photosensitizing drug dihematoporphyrin ether (DHE) on rat subcutaneous arterioles and the modulation of these effects by cyclooxygenase inhibitors indomethacin and acetyl salicylic acid (ASA). Animals received DHE 48 h prior to light activation and additionally either indomethacin, ASA or saline 3 h prior to treatment. Light activation (630 nm, 60 J/cm2) resulted in a significant reduction to 62 +/- 2% SEM of initial blood flow. This effect was inhibited by ASA (98 +/- 8% SEM) and indomethacin (87 +/- 8% SEM). Results from the administration of various doses of both compounds indicate that this inhibition is dose related. The data presented here show that PDT causes a significant reduction in blood flow in normal arterioles and that this effect was inhibited by ASA and indomethacin indicating that prostaglandins or thromboxane A2 may play an important role in the microvascular response to PDT.

Animals↗
PubMed1989

The effect of photodynamic therapy on tumor oxygenation.

Oxygen microelectrodes were used to measure tumor partial pressure of oxygen (PO2) before and after photodynamic therapy (PDT) in a rat transplantable subcutaneous chondrosarcoma. Before PDT there was a gradient of PO2 from the superficial layers of the tumor (PO2 = 46 +/- 6 mm Hg) toward the center of the tumor (PO2 = 10 +/- 1 mm Hg). Mean tumor PO2 (21 +/- 2 mm Hg) was significantly reduced to 3 +/- 1 mm Hg 1 hour after PDT, and this reduction in PO2 persisted 4 hours (8 +/- 2 mm Hg) and 24 hours (6 +/- 1 mm Hg) after PDT. The largest percentage decrease in PO2 occurred at a depth of only 50 microns into the tumor. Inasmuch as PDT has been shown to decrease blood flow, our data suggest that PDT actions on blood vessels in the peripheral areas of the tumor are of major importance for eliciting the tumor hypoxia that contributes to tumor necrosis after PDT.

Animals↗
PubMed1989

A comparison of the effects of photodynamic therapy on normal and tumor blood vessels in the rat microcirculation.

The effects of light activation of the tumor photosensitizer dihematoporphyrin ether (DHE) were studied in the microcirculation of the rat cremaster muscle. Arterioles and venules in an implanted chondrosarcoma were studied by in vivo television microscopy and were compared to normal vessels of the same size elsewhere in the preparation and in control preparations. Activation with green light (530-560 nm, 200 mW/cm2, 120 J/cm2) 48 h after intraperitoneal injection of DHE (10 mg/kg body wt) resulted in significant narrowing of diameters of red blood cell columns in tumor arterioles and venules. The response in normal and control arterioles and venules was not significantly different from that seen in the tumor vessels except that the control arterioles did not remain significantly constricted during the treatment period. Treatment resulted in stasis of blood flow in 90% of tumor and normal arterioles at the completion of light activation. In venules, stasis of blood flow was observed in 75% of tumor and 70% of normal vessels. Vasoconstriction was the primary response in arterioles, while thrombosis predominated in venules. Morphologic assessment of light-activated vessels in the cremaster preparation by transmission electron microscopy revealed platelet aggregation with damage to endothelial cells and smooth muscle cells. Perivascular effects observed included interstitial edema and damage to skeletal muscle cells. In the tumor-bearing preparation, no direct cytotoxic effect on the tumor cells was shown. The surrounding vessels exhibited similar vascular stasis, but the lining cells appeared minimally affected. Photoactivation of DHE results in significant changes in the microcirculation which lead to stasis of blood flow. In this model, the response was similar for the normal microvasculature and for the microcirculation of an implanted chondrosarcoma. These effects may account, in part, for the mechanism of action of photodynamic therapy.

Animals↗
PubMed1988

The effect of photodynamic therapy on the microcirculation.

Photodynamic therapy (PDT) is a new form of cancer therapy involving tumor localization by photosensitizing drugs such as dihematoporphyrin ether (DHE). Light irradiation of drug-sensitized tissue results in photoactivation of DHE and tumor necrosis. The mechanism of action is incompletely understood but involves the generation of singlet oxygen which produces cytotoxic effects on tissues containing the compound. In addition, microcirculatory aberrations have been described during PDT. We have studied the acute effects of PDT on the microcirculation using in vivo television microscopy of the rat cremaster. This has enabled us to observe the effects of PDT on both paired and unpaired arterioles and venules using two different wavelengths of activating light (blue, 450-490 nm, and green, 530-560 nm). For both wavelengths of activating light, significant reduction in blood flow of all vessels was seen during PDT. This, in combination with the formation and embolization of platelet thrombi, resulted in stasis of blood flow in 80% of arterioles and 90% of venules. Observation for 2 hr after the completion of photoactivation revealed reperfusion in 20% of the arterioles but none of the venules. Blood flow was reduced by a combination of vasoconstriction and platelet thrombus formation. Reducing the total activating energy from 120J/cm2 to 24J/cm2 significantly reduced the response in venules and the incidence of stasis in both arterioles and venules. We conclude that the photoactivation of DHE results in significant vasoconstriction and thrombosis of normal vessels and that if these effects are seen at later times after DHE administration and in tumor neovasculature they may contribute to the mechanism by which PDT results in tumor necrosis.

Animals↗
PubMed1988

Effect of photodynamic therapy on blood flow in normal and tumor vessels.

The aim of this series of experiments was to determine the dynamic blood flow changes that occur in normal and neoplastic tissues during photodynamic therapy. Mice bearing SMT-F tumors and rats with transplanted chondrosarcomas were injected with graded doses of dihematoporphyrin ether. Studies of changes in single-vessel and whole-tumor blood flow were carried out with 630 nm light activation. A helium neon laser Doppler velocimeter was used to stimulate dihematoporphyrin ether, as well as to measure changes in flow velocity in both single-vessel and whole-tumor models. There was a reduction of flow velocity in all vessels and tumors in animals injected with 1 to 40 mg/kg dihematoporphyrin ether intraperitoneally. The extent of flow reduction was related to drug dose administered. Decreases in blood flow began within 10 seconds of light stimulation and were maximal within 5 minutes. Both normal and tumor vessels responded similarly. We conclude that photodynamic therapy leads to significant microcirculatory changes that may be pertinent to the mechanism of tumor necrosis.

Animals↗